Lab Notes

Head and Neck Cancer

Overcoming Radiosensitization in Head and Neck Cancer

Matthew Stenger  / May 10, 2016

In a study reported in the Journal of the National Cancer Institute, Eke and colleagues found that simultaneous β1 and epidermal growth factor receptor (EGFR) inhibition resulted in increased cytotoxicity, radiosensitization, and tumor control in human head and neck squamous cell carcinomas. Compar...

Induced Phenotype Targeted Therapy to Overcome Tumor Heterogeneity

Matthew Stenger  / May 10, 2016

In a study reported in the Journal of the National Cancer Institute, Lee and colleagues designed a caspase-3–specific activated prodrug containing doxorubicin linked to a peptide moiety (DEVD-S-DOX), which is cleaved by caspase-3 at apoptosis. Apoptosis was induced in C3H/HeN mammary tumor-bearing m...

Leukemia

Potential Biomarker for Carfilzomib Activity in CLL

Matthew Stenger  / April 25, 2016

Carfilzomib (Kyprolis) is active in B-cell neoplasms but exhibits heterogeneous activity in chronic lymphocytic leukemia (CLL) samples. As reported in Clinical Cancer Research, Lamothe and colleagues examined the mechanism by which carfilzomib induces CLL cell death. In studies using CLL patient sa...

Head and Neck Cancer

PTK2/FAK as Driver of Radioresistance in HPV-Negative Head and Neck Squamous Cell Carcinoma

Matthew Stenger  / April 25, 2016

As reported in Clinical Cancer Research, Skinner and colleagues used proteomic profiling to identify PTK2/FAK as a driver of radioresistance in human papillomavirus (HPV)-negative head and neck squamous cell carcinoma. Using proteomic and transcriptomic analysis of targetable markers, the investiga...

Solid Tumors

Potential Role for HSP70 Peptide Aptamer in Restoring Anticancer Immune Response

Matthew Stenger  / April 25, 2016

Exosomes can activate myeloid-derived suppressor cells via interaction of membrane heat shock protein 70 (HSP70) with Toll-like receptor 2 (TLR2) on the myeloid-derived suppressor cell. As reported in the Journal of the National Cancer Institute, Gobbo and colleagues found that the A8 peptide aptame...

Prostate Cancer

Choline Kinase Alpha as Androgen Receptor Chaperone and Prostate Cancer Target

Matthew Stenger  / April 25, 2016

As reported in the Journal of the National Cancer Institute, Asim and colleagues found that choline kinase alpha (CHKA) acts as a chaperone for the androgen receptor (AR) and may serve as a therapeutic target in prostate cancer. CHKA expression was found to be androgen regulated in cell lines, xeno...

Gynecologic Cancers

High-Accuracy Metabolomic Detection of Early-Stage Ovarian Cancer

Matthew Stenger  / April 25, 2016

As reported in Scientific Reports, Gaul and colleagues used high-performance mass spectrometry to interrogate the serum metabolome of patients with early-stage ovarian cancer and healthy controls. They were able to define a linear support vector machine model of 16 metabolites that identified early-...

Prostate Cancer

Effect of ERG Gene Status on Progression-Free Survival With Abiraterone in Castration-Resistant Prostate Cancer

Matthew Stenger  / June 10, 2015

Gene fusions resulting in androgen receptor–modulated ERG gene overexpression can be found in up to 70% of patients with metastatic castration-resistant prostate cancer. In a study reported in Clinical Cancer Research, Attard and colleagues assessed the effect of ERG rearrangement on outcomes in the...

Gynecologic Cancers

POLE Proofreading Mutations Predict Better Outcome in Endometrial Cancer

Matthew Stenger  / June 10, 2015

In a study reported in the Journal of the National Cancer Institute, Church and colleagues assessed whether proofreading mutations in POLE (which encodes the DNA polymerase epsilon catalytic subunit) were associated with prognosis in endometrial cancer. Such mutations have been reported in approxima...

Ex Vivo Manipulation of Tumor Microenvironment Improves Expansion of Tumor-Infiltrating Lymphocytes for Adoptive Cell Therapy

Matthew Stenger  / June 10, 2015

In a study reported in Clinical Cancer Research, Chacon and colleagues found that ex vivo manipulation of the tumor microenvironment could enhance expansion of tumor-infiltrating lymphocytes for use in adoptive cell therapy. The addition of an agonistic anti–4-1BB antibody during initial tumor frag...

Bispecific Antibody Recruitment to Increase Antitumor Activity of Adoptive T-Cell Transfer

Matthew Stenger  / May 25, 2015

In a study reported in the Journal of the National Cancer Institute, Kobold and colleagues assessed whether combining tumor-specific T cells modified with a marker antigen and a bispecific antibody that selectively recognizes transduced T cells and tumor cells could improve T-cell recruitment to tum...

Colorectal Cancer

IGF2 May Be Target in Colorectal Cancer With Stable Disease As Response  to Anti-EGFR Therapy

Matthew Stenger  / May 25, 2015

In a study exploring the mechanisms of stabilized disease vs tumor regression with targeted anti–epidermal growth factor receptor (EGFR) therapy in colorectal cancer reported in Science Translational Medicine, Zanella and colleagues found that stable disease as response was characterized by overexpr...

CNS Cancers

EGFR Amplification/Overexpression Associated With Improved Response of Glioblastoma to Metronomic Temozolomide

Matthew Stenger  / May 25, 2015

In a study reported in Journal of the National Cancer Institute, Cominelli and colleagues found that EGFR amplification/overexpression was associated with improved response of glioblastoma to adjuvant metronomic (every day of a 28 day cycle at a dosing of 50-75 mg/m2) but not standard (5 consecutive...

Prostate Cancer

'Bipolar' Androgen Therapy in Castration-Resistant Prostate Cancer

Matthew Stenger  / February 10, 2015

Resistance to castrating therapy and androgen deprivation therapy in prostate cancer is due in part to adaptive upregulation of androgen receptor levels by castration-resistant prostate cancer cells in the setting of prolonged exposure to a low-testosterone environment. In a study reported in Scienc...

Lung Cancer

PEDF Improves Lung Cancer Response to Radiation via Vasculature Normalization

Matthew Stenger  / February 10, 2015

In a study reported in Cancer Gene Therapy, Xu and colleagues found that the addition of pigment epithelium-derived factor (PEDF) to radiation improved tumor response in a mouse model of lung cancer. Lewis lung cancer allografts in nude mice were treated with radiation, PEDF, and PEDF plus radiatio...

Lung Cancer

LAMC2 Increases the Metastatic Potential of Lung Adenocarcinoma

Matthew Stenger  / February 10, 2015

Mechanisms of lung cancer metastasis remain largely undefined. In a study reported in Cell Death & Differentiation that used genome-wide transcriptional analysis in a metastasis model, Moon and colleagues found that the epithelial basement membrane protein laminin γ2 (LAMC2) was significantly up...

Gynecologic Cancers

Zoledronic Acid Inhibits Angiogenesis in Ovarian Cancer Patients

Matthew Stenger  / February 10, 2015

The bisphosphonate zoledronic acid has been reported to produce antitumor effects, although the mechanisms of such effects remain unclear. In a study reported in Clinical Cancer Research, Gonzalez-Villasana and colleagues found evidence that zoledronic acid inhibited ovarian cancer angiogenesis by i...

Colorectal Cancer

Therapeutic DNA Vaccination Against Colorectal Cancer via MYB Targeting

Matthew Stenger  / February 10, 2015

The oncoprotein and transcription factor MYB is overexpressed in colorectal cancer and critical to proliferation and tumor cell survival. In a study reported in Clinical & Translational Immunology, Cross and colleagues developed a DNA vaccine to generate an MYB-specific immune response on the hy...

Adding CD47 to Artificial Antigen-Presenting Cells May Stimulate T-Cell Responses and Improve Functionality

Matthew Stenger  / February 10, 2015

Artificial antigen-presenting cells have been shown to stimulate antigen-specific T-cell responses, but their effect in vivo may be compromised by rapid macrophage clearance. In a study reported in Clinical Cancer Research, Bruns and colleagues added CD47 to classic two-signal artificial antigen-pre...

Head and Neck Cancer

Functional Kinomics Identifies WEE1 Kinase as Target in Head and Neck Cancer

Matthew Stenger  / December 15, 2014

In a study reported in Clinical Cancer Research, Moser and colleagues used RNA interference kinase viability screens to identify survival kinases (involved in G2-M cell-cycle checkpoint, SFK, PI3K, and FAK pathways) in p53-mutant head and neck squamous cell carcinoma. Selected kinase targets were te...

Lung Cancer

Lipophilic Bisphosphonate  Plus Rapamycin Active in KRAS-Mutant Lung Cancer

Matthew Stenger  / December 15, 2014

KRAS-mutant lung adenocarcinoma has not been successfully targeted therapeutically. In a study reported in Science Translational Medicine, Xia and colleagues found that the combination of lipophilic bisphosphonates and rapamycin exhibited promising activity in this setting. Lipophilic bisphosphonat...

Gynecologic Cancers

Dual HER2 Targeting Inhibits HER2-Amplified Uterine Serous Carcinoma

Matthew Stenger  / December 15, 2014

In a study reported in Clinical Cancer Research, Groeneweg and colleagues found that dual HER2 targeting showed greater activity than a single agent in HER2-amplified uterine serious carcinoma. In the study, ARK1, ARK2, and SPEC2 cell lines were treated with trastuzumab (Herceptin) or lapatinib (Ty...

Head and Neck Cancer

Intraperitoneal Oxidative Stress Induces Tumoricidal Immune Response in Papillomavirus-Linked Head/Neck Cancer

Matthew Stenger  / December 15, 2014

In a study reported in Clinical Cancer Research, Rossmann and colleagues found that induction of oxidative stress via O3/O2 pneumoperitoneum treatment in the papillomavirus-associated rabbit auricular VX2 carcinoma model of head and neck cancer resulted in a tumoricidal immune response that could be...

Solid Tumors

Checkpoint Blockade Immunotherapy Targets Tumor-Specific Mutant Antigens

Matthew Stenger  / December 15, 2014

In a study reported in Nature, Gubin and colleagues showed that the effects of CTLA-4 (cytotoxic T-lymphocyte–associated protein-4) and PD-1 PD-1 (programmed cell death protein-1) inhibitors (checkpoint blockade) are achieved through targeting of tumor-specific mutant antigens. In the study, genomic...

Pancreatic Cancer

WEE1 Inhibition Sensitizes Pancreatic Cancer to PARP Inhibitor Radiosensitization

Matthew Stenger  / December 15, 2014

In a study reported in Clinical Cancer Research, Karnak and colleagues found that WEE1 kinase inhibition increased the sensitivity of pancreas cancer to the radiosensitizing effects of poly(ADP-ribose) polymerase (PARP) inhibition. Treatment of human pancreatic cancer AsPC-1 and MiaPaCa-2 cells wit...

PD-L1 Expression by Tumor-Infiltrating Cells Associated With Activity of Anti–PD-L1 Antibody in Multiple Cancer Types

Matthew Stenger  / December 15, 2014

Programmed cell death protein ligand 1 (PD-L1) interferes with anticancer immune response by binding programmed PD-1 and B7.1 (CD80), negative regulators of T-cell activation. In a study reported in Nature, Herbst and colleagues showed that treatment with an anti–PD-L1 antibody (MPDL3280A) produced ...

Solid Tumors

Predicting Immunogenic Tumor Neoantigens With Combined Mass Spectrometry and Exome Sequencing

Matthew Stenger  / December 15, 2014

Peptides containing tumor somatic mutations are potentially immunogenic if presented on major histocompatibility complex class I molecules (MHC-I), and it has been shown that such mutant peptides act as T-cell epitopes.  In a study reported in Nature, Yadav and colleagues developed an approach combi...

Antitumor Effect of Intratumoral Injection of Clostridium Spores

Matthew Stenger  / December 1, 2014

Species of Clostridium bacteria have been shown to kill tumor cells growing under hypoxic conditions. In a study reported in Science Translational Medicine, Roberts and colleagues showed that intratumoral injection of an attenuated strain of Clostridium novyi (C novyi-NT) produced a microscopically ...

Pancreatic Cancer

Mitochondrial Respiration as Target in KRAS-Mutant Pancreatic Cancer

Matthew Stenger  / December 1, 2014

Targeting of oncogenes can produce tumor shrinkage, but the frequency of relapse indicates that a population of tumor cells survives oncogene inhibition. In a study in a KRAS-mutant pancreatic ductal adenocarcinoma mouse model reported in Nature, Viale and colleagues found that a subpopulation of do...

Solid Tumors

Selective Generation of Reactive Oxygen Species in Tumor Cells

Matthew Stenger  / December 1, 2014

In a study reported in Clinical Cancer Research, Shin and colleagues synthesized a novel polyphenol conjugate (DPP-23) that exerted antitumor effects by targeting the unfolded protein response in the endoplasmic reticulum via production of reactive oxygen species in cancer cells but not in normal ce...

Issues in Oncology

PRC2 Loss Amplifies RAS-Driven Transcription and Results in Sensitivity to Bromodomain Inhibition

Matthew Stenger  / December 1, 2014

PRC2 (polycomb repressive complex 2) has been shown to promote oncogenesis in many tumor types; however, loss of function mutations in PRC2 components has also been shown to occur in some hematopoietic malignancies, raising questions about the precise role of the complex in cancer. In a study repor...

Hyperthermia Reduces Gemcitabine Resistance

Matthew Stenger  / December 1, 2014

Removal of incorporated gemcitabine by DNA repair mechanisms may contribute to resistance to the agent in solid tumors. In a study reported in Journal of the National Cancer Institute, Raoof and colleagues found that radiofrequency-induced hyperthermia blocked repair of gemcitabine-stalled replicati...

Breast Cancer
Issues in Oncology

Single-Nucleus Genome Sequencing Shows Early Aneuploid Rearrangement and Gradual Clonal Evolution in Breast Cancer

Matthew Stenger  / December 1, 2014

In a study reported in Nature, Wang and colleagues developed a whole-genome and exome single-cell sequencing approach (nuc-seq) using G2/M nuclei and used the method to sequence single normal and tumor nuclei from an estrogen receptor–positive breast cancer and a triple-negative ductal carcinoma. Th...

Head and Neck Cancer
Issues in Oncology

mTOR Cotargeting Active in Cetuximab-Resistant Head/Neck Cancers With PIK3CA and RAS Mutations

Matthew Stenger  / December 1, 2014

In a study reported in Journal of the National Cancer Institute, Wang and colleagues found that adding an mTOR inhibitor to cetuximab (Erbitux) resulted in marked improvement in antitumor activity in squamous cell carcinomas of the head and neck expressing PIK3CA and RAS oncogenes. Cetuximab treatm...

Breast Cancer

RNA-Binding Protein Destabilizes Transcripts of Novel Metastasis Suppressor Genes in Breast Cancer

Matthew Stenger  / November 15, 2014

In a study reported in Nature, Goodarzi and colleagues attempted to identify post-transcriptional modulators of mRNA stability in breast cancer via whole-genome transcript stability measurements in poorly and highly metastatic isogenic human breast cancers. They identified a family of structural RNA...

Breast Cancer

Potential Roles for Metformin and Everolimus in Obese Women With ER-Positive Breast Cancer

Matthew Stenger  / November 15, 2014

Obesity increases the risk of breast cancer death in postmenopausal women with estrogen receptor (ER)-positive breast cancer, although underlying mechanisms remain unclear. In studies reported in the Journal of the National Cancer Institute, Fuentes-Mattei and colleagues identified an association of...

Colorectal Cancer
Pancreatic Cancer

Peripheral Nerve Schwann Cells Migrate to Pancreas and Colon Cancer Cells Before Invasion

Matthew Stenger  / November 15, 2014

In a study reported in the Journal of the National Cancer Institute,  Demir and colleagues used novel three-dimensional migration and Schwann cell outgrowth assays to monitor the timing and specificity of Schwann cell migration and cancer invasion toward peripheral neurons through digital time-lapse...

Breast Cancer

DNA Double-Strand Break Repair Genes and Oxidative Damage in Brain Metastasis of Breast Cancer

Matthew Stenger  / November 15, 2014

In a study reported in the Journal of the National Cancer Institute, Woditschka and colleagues identified a role for the DNA repair genes BARD1 and RAD51 and oxidative damage in brain metastases in breast cancer. The two genes were implicated in expression profiling of 23 matched resected brain meta...

Breast Cancer

Suppressor of Cytokine Signaling Protein Promotes Breast Cancer Recurrence by Potentiating c-MET Signaling

Matthew Stenger  / November 15, 2014

Breast cancer mortality is primarily due to tumor recurrence. In a study reported in Cancer Discovery, Feng and colleagues found that the suppressor of cytokine signaling protein SPSB1 is spontaneously upregulated in mammary tumor recurrence and is both necessary and sufficient to promote tumor recu...

Leukemia

Sonic Hedgehog Factor GLI1 Induces Resistance to Cytarabine and Ribavirin in AML via Glucuronidation

Matthew Stenger  / November 15, 2014

Responses to cytarabine-based therapy in acute myeloid leukemia (AML) are often of short duration. Ribavirin has been used to inhibit the eukaryotic translation initiation factor (eIF4E) and has produced responses, including remissions, in AML, but relapse invariably occurs. As reported in Nature, ...

CNS Cancers

Effect of Micro-RNA on M2 Macrophages and Murine Glioblastoma

Matthew Stenger  / November 15, 2014

Monocyte-derived glioma-associated macrophages are the largest infiltrating immune cell population in glioblastomas and act to facilitate gliomagenesis. In a study reported in the Journal of the National Cancer Institute, Xu and colleagues assessed the effect of microRNA (miR)-142-3p on proinflammat...

Bladder Cancer

EGFR a Potential Target in Muscle-Invasive Bladder Cancer With Basal-Like Phenotype

Matthew Stenger  / November 1, 2014

As reported by Rebouissou and colleagues in Science Translational Medicine, a subset of muscle-invasive bladder cancers that present with a basal-like phenotype is associated with poorer survival, EGFR pathway activation, and sensitivity to EGFR inhibition. Assessment of data from 383 tumors reveal...

Supportive Care

MHC-Matched Graft-vs-Host Disease Requires Recipient Intestinal Barrier Loss and Natural Killer Cell Inactivation

Matthew Stenger  / November 1, 2014

Although available data indicate an association among pretransplantation conditioning intensity, intestinal barrier loss, and severity of graft-vs-host disease, the multiple effects of irradiation and other types of conditioning have made it difficult to precisely identify the role of intestinal bar...

Hepatobiliary Cancer

Successful Immunotherapy With Mutation-Specific CD4-Positive T Cells in Patient With Epithelial Cancer

Matthew Stenger  / November 1, 2014

There is limited evidence of mutation-specific T-cell response to epithelial cancers. In a study reported in Science, Tran and colleagues used whole-exome sequencing to show that tumor-infiltrating lymphocytes included CD4-positive Th1 cells that recognized a mutation in erbb2 interacting protein (E...

Chemotherapy-Induced Immunosuppressive Myeloid Cells Inhibit Tumor Control via PD-1–PD-L1 Axis

Matthew Stenger  / November 1, 2014

In a study reported in Cancer Research, Ding and colleagues identified mechanisms by which cyclophosphamide induces suppressor cells that inhibit immune response and predispose to loss of tumor control. They found that cyclophosphamide treatment induces expansion of inflammatory monocytic myeloid ce...

Prostate Cancer

Androgen, Estrogen, and Stem Cell Markers Help Predict Recurrence and Survival in Metastatic Prostate Cancer

Matthew Stenger  / November 1, 2014

In a study reported in Clinical Cancer Research, Fujimura and colleagues developed and tested models to predict prostate-specific antigen (PSA) recurrence and cancer-specific survival in patients with treatment-naive prostate cancer and bone metastases using mRNA expression of genes involved in andr...

Colorectal Cancer

Polymorphisms and Cetuximab Benefit in Locally Advanced Rectal Cancer

Matthew Stenger  / November 1, 2014

Polymorphisms in FcγR (receptor for the constant region of immunoglobulin G) have been reported to be associated with improved immune-mediated effects of cetuximab (Erbitux) in metastatic colorectal cancer. In a study reported in Clinical Cancer Research, Sclafani and colleagues analyzed the associa...

Breast Cancer

Tumor PD-L1 mRNA Expression Associated With Improved Outcome in Breast Cancer

Matthew Stenger  / October 15, 2014

Inhibition of the PD-1/PD-ligand1 (PD-L1) axis has shown considerable therapeutic promise in several cancers. Tumor PD-L1 protein expression may predict response to drugs targeting this pathway, but its measurement has been limited by the lack of standardized immunohistochemical methods and variable...

Head and Neck Cancer

TP53 Mutation Associated With Chromosome 3p Loss in Head and Neck Squamous Cell Carcinoma

Matthew Stenger  / October 15, 2014

In an analysis of molecular and clinical features associated with survival in head and neck squamous cell carcinoma reported in Nature Genetics, Gross and colleagues found that the TP53 mutation is frequently accompanied by loss of chromosome 3p; the combination of these alterations was associated w...

Gastrointestinal Cancer

CD44 Expression a Marker for Chemotherapy Resistance in Gastric Cancer, Overcome by Hedgehog Inhibition

Matthew Stenger  / October 15, 2014

CD44 is a gastric cancer stem cell marker, and the hedgehog signaling pathway can be dysregulated by cancer stem cells during tumorigenesis. In a study reported in Clinical Cancer Research, Yoon and colleagues found that high CD44 expression was associated with chemotherapy resistance and poorer sur...

Issues in Oncology

Potential for Improved Effectiveness and Reduced Toxicity of Radiotherapy With Ultrahigh Dose-Rate FLASH Irradiation

Matthew Stenger  / October 15, 2014

Studies in vitro have suggested that sub-millisecond pulses of radiation produce less genomic instability than continuous prolonged irradiation at the same total dose. In a study reported in Science Translational Medicine, Favaudon and colleagues assessed the effects of ultrahigh dose-rate irradiati...

CNS Cancers

Dissemination of Glioblastoma Multiforme Outside Brain Is Common

Matthew Stenger  / October 15, 2014

The finding of extracranial metastases after organ transplantation from glioblastoma multiforme donors raised issues with the notion that disease spread is restricted to the brain. In a study reported in Science Translational Medicine, Müller and colleagues found that hematogenous spread of glioblas...

CNS Cancers

MSH6 Mutations May Influence Temozolomide Resistance in Treatment-Naive Gliomas Independent of MGMT Methylation

Matthew Stenger  / October 15, 2014

Resistance to temozolomide in glioblastoma has been thought to be largely mediated by expression of the DNA repair enzyme MGMT, although there are data suggesting a role for inactivation of MSH6 and other mismatch repair proteins. In a study reported in Clinical Cancer Research, Nguyen and colleagu...

Breast Cancer

Different Transcriptional Responses to Fulvestrant and Estrogen Deprivation in ER-Positive Breast Cancer

Matthew Stenger  / October 15, 2014

In a study reported in Clinical Cancer Research, Patani and colleagues investigated whether distinct transcriptional responses were associated with the reported increased effectiveness of the estrogen receptor (ER) antagonist fulvestrant (Faslodex) over the aromatase inhibitor anastrozole in ER-posi...

Breast Cancer
Gastroesophageal Cancer

TRIM44 Amplification in Esophagogastric, Breast Tumors May Be Marker for mTOR Inhibitor Therapy

Matthew Stenger  / September 15, 2014

TRIM44 family overexpression is associated with carcinogenesis, and TRIM44 has been identified as a prognostic gene. In a study reported in Journal of the National Cancer Institute, Ong and colleagues attempted to identify therapeutic strategies for patients with TRIM44 overexpression. Genomic and ...

Issues in Oncology

Extracellular Matrix Stiffness Promotes Malignant Progression Via PTEN-Reducing Effect of Micro-RNA

Matthew Stenger  / September 15, 2014

Tissue mechanics are altered in tumor progression, although many of the mechanisms underlying the changes remain unclear. In a study reported in Nature Medicine, Mouw and colleagues found that increased tissue extracellular matrix stiffness modulated microRNA expression to promote tumor progression ...

Colorectal Cancer

Potential Marker for Response to Anti-EGFR Therapy in KRAS Wild-Type Metastatic Colorectal Cancer

Matthew Stenger  / September 15, 2014

As reported in Clinical Cancer Research, Manceau and colleagues attempted to identify microRNAs that can predict response to anti-EGFR therapy in wild-type KRAS metastatic colorectal cancer patients. Initial screening of 1,145 microRNAs in fresh frozen tumor samples from chemotherapy-refractory met...

Leukemia

Tissue Microenvironment Affects Activity of PTEN in Leukemia

Matthew Stenger  / September 15, 2014

The tumor suppressor PTEN, which is underexpressed in many cancers, dephosphorylates phosphatidylinositol (3,4,5)-triphosphate and thus inhibits activity of phosphatidylinositol 3-kinases involved in growth factor and survival factor signaling through effectors such as Akt and mTOR. As reported in N...

Colorectal Cancer

Overexpression of Sirt7 Is Associated With Tumorigenesis and Poor Prognosis in Colorectal Cancer

Matthew Stenger  / September 15, 2014

Sirt7, a member of the sirutin family, is overexpressed in some cancers. In a study of the potential role of Sirt7 in colorectal cancer reported in Clinical Cancer Research, Yu and colleagues found that increased Sirt7 protein level in colorectal cancer tissue was associated with higher tumor stage ...

Lung Cancer

Remarkable Response to Sorafenib in Advanced Lung Adenocarcinoma and Oncogenic ARAF Mutation

Matthew Stenger  / September 15, 2014

As reported in Journal of Clinical Investigation by Imielinski and colleagues, whole-genome and RNA sequencing of tumor and normal tissue in a patient with advanced lung adenocarcinoma who exhibited a remarkable response to sorafenib (Nexavar) revealed a somatic ARAF S214 mutation expressed at high ...

Colorectal Cancer

LCS6 Genotype Not Associated With KRAS Mutation Status or Outcome in Stage III Colon Cancer

Matthew Stenger  / September 15, 2014

A let-7 microRNA-complementary site (LCS6) polymorphism in the 3’UTR of KRAS has been shown to disrupt let-7 binding and upregulate KRAS expression. As reported in Clinical Cancer Research, Sha and colleagues found that LCS6 genotype was not associated with KRAS mutation status or disease-free survi...

Skin Cancer

PD-1 Identifies Patient-Specific CD8-Positive Tumor-Infiltrating Lymphocytes in Melanoma

Matthew Stenger  / September 15, 2014

Adoptive transfer of tumor-infiltrating lymphocytes can mediate regression of metastatic melanoma. However, there are no effective markers to identify and select patient-specific repertoires of tumor-reactive and mutation-specific CD8-positive lymphocytes, limiting the ability to develop strategies ...

Multiple Myeloma

Modification of T Cells to Target CS1 Improves Eradication of Myeloma Cells

Matthew Stenger  / September 15, 2014

CS1 is a cell surface glycoprotein that appears to be highly expressed on myeloma cells and less expressed on normal cells; CS1 overexpression has been found to promote myeloma cell growth and survival by increasing myeloma adhesion to bone marrow stromal cells and increasing myeloma colony formatio...

Solid Tumors

Potential for Therapeutic Autovaccination Against Solid Tumors With Intratumoral Poly-ICLC

Matthew Stenger  / September 15, 2014

In a study reported in Cancer Immunology Research, Salazar and colleagues found a remarkable response to a strategy of sequential intratumoral and intramuscular injections of the stabilized dsRNA viral mimic and pathogen-associated molecular pattern (PAMP) polyinosinic-polycytidylic acid-polylysine-...

Prostate Cancer

BET Bromodomain Inhibition Highly Active in Castration-Resistant Prostate Cancer

Matthew Stenger  / September 1, 2014

Progression to castration-resistant prostate cancer after androgen ablation therapy is primarily due to deregulated androgen receptor signaling. Treatment with agents that target such signaling, such as abiraterone (Zytiga) and enzalutamide (Xtandi), has been successful. However, durable response is...

Fusion Protein Improves Dendritic Cell Penetration, Raising Prospect of Efficient Cancer Vaccine

Matthew Stenger  / September 1, 2014

Immunotherapy with dendritic cells in combination with cytotoxic chemotherapy may eliminate minimal disease burden by generating cytotoxic T lymphocytes (CTLs). Improving the cytosolic bioavailability of tumor-specific antigens to improve access to HLA class I molecules would result in better genera...

Dysregulated Cell-Cycle Progression and Akt Hyperactivation in Cancer

Matthew Stenger  / September 1, 2014

Akt plays important roles in cell proliferation, survival, and metabolism. Akt hyperactivation contributes to tumorigenesis and is associated with poor prognosis and resistance to chemotherapy and radiotherapy. It is known that activation of Akt results from phosphorylation at S473 and T308, but it ...

CNS Cancers

Small Molecule Induces Catastrophic Vacuolization and Death of Glioblastoma Cells

Matthew Stenger  / September 1, 2014

In a study reported in Cell, Kitambi and colleagues screened patient-derived glioblastoma cells to identify targetable cellular processes gained by these cells that are not necessarily involved in malignancy. They found that a quinine derivative (NSC13316) selectively compromised viability of gliobl...

Colorectal Cancer

15-PGDH Expression in Normal Mucosa May Be Biomarker for Aspirin Prevention of Colorectal Cancer

Matthew Stenger  / September 1, 2014

Aspirin use reduces the risk of colorectal cancer at least in part via inhibition of prostaglandin-endoperoxide synthase 2 (PTGS2, COX-2) pathways. Hydroxyprostaglandin dehydrogenase 15-(nicotinamide adenine dinucleotide; 15-PGDH, HPGD) is a metabolic antagonist of PTGS2 and is downregulated in colo...

Leukemia

Spleen Tyrosine Kinase Inhibition Has Promise in High-Risk Precursor B-Cell ALL

Matthew Stenger  / August 15, 2014

In a study reported in Science Translational Medicine, Perova and colleagues found that pre–B-cell receptor–independent spleen tyrosine kinase signaling was necessary for leukemic B-cell survival and proliferation in a mouse model. Investigation of samples from pediatric and adult B-cell acute lymph...

Breast Cancer

BRCA2 Inhibits Genome Instability by Preventing R-Loop Accumulation

Matthew Stenger  / August 15, 2014

Genome instability and DNA damage in cancer can be induced by mutations in genes involved in pre-mRNA splicing and biogenesis and export of messenger ribonucleoprotein (mRNP). Instability can be mediated by R-loops formed by DNA-RNA hybrids and displaced single-stranded DNA. The TREX-2 complex is i...

Solid Tumors

Prolyl Hydroxylase Inhibition Protects Against Gastrointestinal Radiation Toxicity

Matthew Stenger  / August 15, 2014

In a study reported in Science Translational Medicine, Taniguchi and colleagues found that inhibition of prolyl hydroxylase by genetic knockout or inhibition of all prolyl hydroxylase domain isoforms by the small-molecule dimethyloxallyl glycine (DMOG) resulted in promotion of protection against rad...

Skin Cancer

FBXW7 as Tumor Suppressor and NOTCH1 Inhibition as Potential Strategy in Melanoma

Matthew Stenger  / August 15, 2014

In a study reported in the Journal of the National Cancer Institute, Aydin and colleagues found that mutation in and inactivation of FBXW7 and accumulation of NOTCH1, a substrate of FBXW7, were associated with melanoma tumorigenesis. FBXW7 was found to be mutated in 8% of 103 melanoma patients, and...

CNS Cancers

Mesenchymal Stem Cells With Oncolytic HSV Variants Promising in Glioblastoma Multiforme

Matthew Stenger  / August 15, 2014

Although oncolytic herpes simplex virus (HSV) has been found to be safe in clinical trials in malignant glioblastoma multiforme, its efficacy is limited by insufficient viral spread after tumor resection. In a study reported in the Journal of the National Cancer Institute, Duebgen and colleagues sho...

Prostate Cancer

Mutations in IGF Pathway Genes Associated With Prostate Cancer Mortality

Matthew Stenger  / August 15, 2014

In a study reported in the Journal of the National Cancer Institute, Cao and colleagues identified mutations in insulin-like growth factor (IGF) pathway genes that were significantly associated with mortality in prostate cancer. Analysis of 530 single nucleotide polymorphisms (SNPs) in 26 IGF pathw...

Solid Tumors
Skin Cancer

Melanoma Metastases Exhibit Site-Specific Antigen Heterogeneity Correlating With T-Cell Infiltration

Matthew Stenger  / August 15, 2014

In a study reported in Clinical Cancer Research, Bartlett and colleagues found that melanoma metastases exhibit site-specific antigen heterogeneity that correlates with T-cell infiltration. A total of 3,086 metastatic tumors involving various anatomic sites were assessed for a panel of melanocyte d...

Breast Cancer

Plasma Tumor DNA Detectable Before and After Surgery in Patients with Early-Stage Breast Cancer

Matthew Stenger  / August 15, 2014

Detecting circulating plasma tumor DNA in patients with early-stage cancer has the potential to influence selection of adjuvant systemic therapy. In a study reported in Clinical Cancer Research, Beaver and colleagues found that plasma tumor DNA could be detected both before and after surgery in pati...

Gastroesophageal Cancer

IGF-2/IGF-1R Inhibition Shows Promise in Esophageal Cancer

Matthew Stenger  / August 15, 2014

In a study reported in Clinical Cancer Research, Li and colleagues found that overexpression of Id1 protein resulted in insulin-like growth factor (IGF)-2 production, which, in turn, resulted in esophageal cancer cell proliferation, survival, and invasion via autocrine activation of AKT. Overexpres...

Breast Cancer

Centrosome Amplification Promotes Cellular Invasion in Mammary Epithelial Cells

Matthew Stenger  / August 15, 2014

Centrosomes, the primary microtubule organizing centers within cells, are commonly amplified in tumors, but the role of centrosome amplification in tumorigenesis is unclear. Centrosome amplification is not favored in nontransformed cells, with extra centrosomes being spontaneously lost in the absenc...

MTH1 Inhibition Blocks Sanitation of Deoxyribonucleotide Triphosphate Pool and Causes Cancer Cell Death

Matthew Stenger  / July 25, 2014

Dysfunctional redox regulation in cancer results in production of reactive oxygen species, damaging DNA and free deoxyribonucleotide triphosphates (dNTPs). The MTH1 protein, which is nonessential in normal cells, sanitizes oxidized dNTP pools, preventing incorporation of damaged bases during DNA rep...

Colorectal Cancer

High Macrophage Inhibitory Cytokine-1 Levels and Colorectal Cancer Risk

Matthew Stenger  / July 25, 2014

Chronic inflammation is implicated in the development of colorectal cancer, and the plasma inflammatory biomarker macrophage inhibitory cytokine-1 (MIC-1, GDF15) may have a direct role in tumorigenesis. As reported in Journal of the National Cancer Institute, Mehta and colleagues found that subject...

EGFR Activation Increases Cancer Cell ‘Visibility’ for Cytotoxic T Lymphocytes

Matthew Stenger  / July 25, 2014

The antitumor activities of cytolytic T lymphocytes and natural killer cells are being increasingly investigated and exploited in cancer immunotherapy. One mechanism by which these cells recognize tumor cells is by engagement of NKG2D, an activating receptor on cytolytic T lymphocytes and natural ki...

Vaccine Targeting Tumor Antigen to Dendritic Cell Receptors Induces Antigen-Specific Immunity

Matthew Stenger  / July 25, 2014

Anticancer immunity may be enhanced by harnessing the ability of dendritic cells to initiate T-cell immunity through efficient uptake and presentation of endocytosed material. In preclinical models, delivery of tumor-associated antigens to dendritic cells using receptor-specific monoclonal antibodie...

Colorectal Cancer

Aflibercept More Active Than Bevacizumab in Patient-Derived Colorectal Cancer Xenografts

Matthew Stenger  / June 25, 2014

Some evidence suggests that dual targeting of vascular endothelial growth factor (VEGF) and placental growth factor (which binds to VEGFR-1) might provide more effective antiangiogenic therapy. In a study reported in Molecular Cancer Therapeutics, Chiron and colleagues compared the antitumor effects...

Copper Chelation for BRAF-Mutated Disease?

Matthew Stenger  / June 10, 2014

The V600E mutation in BRAF kinase is associated with oncogenesis in melanoma and other cancers. BRAF V600E phosphorylates and activates MEK1 and MEK2 kinases, which phosphorylate and activate ERK1 and ERK2 kinases, resulting in activation of the MAPK pathway. The addition of a BRAF V600E inhibitor t...

MTH1 Inhibition Blocks Sanitation of Deoxyribonucleotide Triphosphate Pool and Causes Cancer Cell Death

Matthew Stenger  / June 10, 2014

Dysfunctional redox regulation in cancer results in production of reactive oxygen species, damaging DNA and free deoxyribonucleotide triphosphates (dNTPs). The MTH1 protein, which is nonessential in normal cells, sanitizes oxidized dNTP pools, preventing incorporation of damaged bases during DNA rep...

Lung Cancer

Druggable Oncogene Fusions Found in KRAS Wild-Type Lung Invasive Mucinous Adenocarcinoma

Matthew Stenger  / June 10, 2014

As reported in Clinical Cancer Research, Nakaoku and colleagues identified oncogene fusions that function as driver mutations in KRAS wild-type invasive mucinous adenocarcinoma of the lung. Whole-transcriptome sequencing of 32 invasive mucinous adenocarcinomas, including 27 without KRAS mutations, ...

Colorectal Cancer

High Macrophage Inhibitory Cytokine-1 Levels and Colorectal Cancer Risk

Matthew Stenger  / June 10, 2014

Chronic inflammation is implicated in the development of colorectal cancer, and the plasma inflammatory biomarker macrophage inhibitory cytokine-1 (MIC-1, GDF15) may have a direct role in tumorigenesis. As reported in Journal of the National Cancer Institute, Mehta and colleagues found that subject...

Colorectal Cancer

PPAR-δ/β Overexpression Increases Colon Tumorigenesis

Matthew Stenger  / May 15, 2014

Although it is known that nuclear receptor peroxisome proliferator-activated receptor-δ/β (PPAR-d) is upregulated in colorectal cancer, the role of PPAR-d in tumorigenesis remains uncertain. In a study reported in Journal of the National Cancer Institute, Zuo and colleagues developed a mouse model o...

Solid Tumors

Inactivation of E3 Ubiquitin Ligase Cbl-b Allows Natural Killer Cells to Control Metastases

Matthew Stenger  / May 15, 2014

New therapeutic approaches to blocking inhibitory pathways of the immune system have raised hopes that such treatments might thwart development of metastases. In a study in Nature, Paolino and colleagues have shown that genetic deletion of the E3 ubiquitin ligase Cbl-b (casitas B-lineage lymphoma-b)...

Colorectal Cancer

IL-15 Deletion Linked to Reduced Local Proliferation of B and T Cells and Poorer Outcome in Colorectal Cancer

Matthew Stenger  / May 15, 2014

The tumor microenvironment contains a complex network of cytokines that contribute to the nature of intratumoral immune reactions. In a study reported in Science Translational Medicine, Mlecnik and colleagues assessed chromosomal gains and losses and expression of 59 cytokines and receptors and thei...

Colorectal Cancer

IL-17A Promotes and GM-CSF Suppresses Circulating Tumor Cells and Metastasis in Colorectal Cancer

Matthew Stenger  / May 15, 2014

In a study of the roles of interleukin (IL)-17A and circulating tumor cells in colorectal cancer metastasis, Tseng and colleagues measured mesenteric circulating tumor cells according to colorectal cancer stage in patients and assessed the interaction of circulating tumor cells and IL-17A in a mouse...

Breast Cancer

Epigenetic Reprogramming of HOXC10 Results in Endocrine Resistance in Breast Cancer

Matthew Stenger  / May 15, 2014

Resistance to aromatase inhibitors is a major problem in treatment of estrogen receptor (ER)-positive breast cancer. In a study reported in Science Translational Medicine, Pathiraja and colleagues found pervasive DNA hyper- and hypomethylation and enrichment for promoter hypermethylation of developm...

Solid Tumors

DNA Repair Pathway Recombination Proficiency Score Correlates With Tumor Sensitivity to Chemotherapy

Matthew Stenger  / May 15, 2014

As reported in Science Translational Medicine, Pitroda and colleagues developed a recombination proficiency score that measures the efficiency of DNA repair pathways in the context of cancer therapy aimed at generating DNA damage. The score is based on expression levels of four genes involved in DNA...

Solid Tumors

New p53-Dependent Gene Cooperates With p53 in Tumor-Suppressor Functions

Matthew Stenger  / May 15, 2014

The TP53 tumor-suppressor gene influences genomic stability, apoptosis, autophagy, response to stress, and DNA damage, and identification of new p53-target genes could help elucidate mechanisms through which p53 controls cell integrity and response to damage. As reported in Journal of the National C...

Leukemia

Synergy of IAP Antagonist and Demethylating Agents Against AML Stem/Progenitor Cells

Matthew Stenger  / April 15, 2014

In a study reported in the Journal of the National Cancer Institute, Carter and colleagues identified deregulated apoptotic components in acute myeloid leukemia (AML) stem/progenitor cells and investigated the effects of the novel inhibitor of apoptosis (IAP) protein antagonist and SMAC mimetic biri...

Lung Cancer

Antioxidants Accelerate Lung Cancer Progression and Reduce Survival in Mice

Matthew Stenger  / April 15, 2014

Clinical trials of antioxidants in cancer have yielded inconsistent results. In a study reported in Science Translational Medicine, Sayin and colleagues evaluated the effects of the antioxidants N-acetylcysteine and vitamin E in mouse models of BRAF- and KRAS-induced lung cancer. N-acetylcysteine an...

CNS Cancers

Mutation Predicts Benefit From Alkylating Chemotherapy in Oligodendroglial Tumors

Matthew Stenger  / April 15, 2014

Patients in the Radiation Therapy Oncology Group (RTOG) 9402 study with 1p/19q codeleted anaplastic oligodendroglial tumors had markedly prolonged overall survival after chemoradiotherapy (with procarbazine, lomustine, and vincristine) compared with radiation therapy alone. Some patients with noncod...

Solid Tumors

shRNAs Can Identify T-Cell Inhibitory Mechanisms in Tumor Microenvironment

Matthew Stenger  / April 15, 2014

Although recent findings indicate that targeting of inhibitory receptors on T cells can produce durable responses in some cancer patients despite the presence of advanced disease, the mechanisms controlling T-cell function in immunosuppressive tumors have not been well characterized. In a study repo...

Multiple Myeloma

Lenalidomide Acts in Myeloma by Degrading Lymphoid Transcription Factors IKZF1 and IKZF3

Matthew Stenger  / April 15, 2014

The mechanism of action of lenalidomide (Revlimid) in multiple myeloma and other B-cell neoplasms remains largely uncharacterized. In a study reported in Science, Krönke and colleagues identified one of the effects of lenalidomide in this setting. Use of quantitative proteomics showed that lenalido...

Solid Tumors

Antitumor Activity of  Poly-IC and Anti–PD-L1 Monoclonal Antibody

Matthew Stenger  / March 15, 2014

Epitope-based vaccines that induce CD8-positive T-cell responses to tumor-associated antigens are being investigated in the treatment of several types of cancer. In a study reported in Clinical Cancer Research, Nagato and colleagues showed that combined immunotherapy with polyinosinic-polycytidylic ...

CNS Cancers

Dual PI3K/mTOR Inhibitor Effective as Radiosensitizer for Glioblastoma

Matthew Stenger  / March 15, 2014

In a study reported in Clinical Cancer Research, del Alcazar and colleagues assessed the effects of the dual PI3K/mTOR inhibitor NVP-BEZ235 as a radiosensitizer in glioblastoma. No DNA double-strand break repair inhibitors have been successful in treating glioblastoma. However, in prior studies in v...

Solid Tumors

Antitumor Immunity Affected by Standard Lab Mouse Housing Temperature

Matthew Stenger  / March 15, 2014

In a study reported in Proceedings of the National Academy of Sciences USA, Kokolusa and colleagues showed that fundamental aspects of antitumor immunity are significantly affected by ambient housing temperature for lab mice. Standard ambient temperature in research facility lab mice housing is 20°...

Colorectal Cancer

Decreased Diversity of Gut Bacteria Associated With  Risk of Colorectal Cancer

Matthew Stenger  / March 15, 2014

In a study reported in the Journal of the National Cancer Institute, Ahn and colleagues found that decreased diversity of gut bacteria and differences in levels of specific bacteria were associated with significantly increased risk of colorectal cancer. The study involved measurement of 16S ribosom...

Lung Cancer

Protein Expression–Based Risk Model for Recurrence in Resected NSCLC

Matthew Stenger  / March 15, 2014

In a study reported in Clinical Cancer Research, Gold and colleagues developed a risk model for recurrence of resected non–small cell lung cancer (NSCLC) based on protein expression and clinical variables. The study involved analysis of samples from 370 patients with NSCLC resected between 2002 and...

CD137 Identifies and Enriches for Tumor-Reactive T Cells

Matthew Stenger  / March 15, 2014

In a study reported in Clinical Cancer Research, Ye and colleagues showed that CD137 can be used to identify tumor-reactive T cells and to enrich for tumor-infiltrating lymphocytes and tumor-associated lymphocytes for use in adoptive immunotherapy. In the study, tumor-infiltrating lymphocytes from ...

Solid Tumors

Intact Gut Microbe Populations Improve Response to Chemotherapy

Matthew Stenger  / February 15, 2014

Gut microflora affect local and systemic inflammatory responses, and inflammation is involved in both pathogenesis and treatment of cancers, but it is unclear whether gut microflora affect inflammation in the sterile tumor microenvironment. In a study reported in Science, Iida and colleagues assesse...

Solid Tumors

Effect of Cyclophosphamide Mediated by Gut Microflora

Matthew Stenger  / February 15, 2014

In a study reported in Science, Viaud and colleagues showed that the antitumor activity of cyclophosphamide is dependent on the effect of this agent on gut microflora. In mouse studies, the investigators found that cyclophosphamide altered the composition of microbiota in the small intestine, induc...

Pancreatic Cancer

CYB5A Induces Autophagy, and Higher Expression Improves Survival in Pancreatic Cancer

Matthew Stenger  / February 15, 2014

Loss of 18q22.3 is a prognostic marker in pancreatic ductal adenocarcinoma. In a study reported in the Journal of the National Cancer Institute, Giovannetti and colleagues assessed the role of 18q22.3-encoded CYB5A in pancreatic cancer prognosis and autophagy modulation. In the study, both resected...

Colorectal Cancer

High Plasma Alkylresorcinols Associated With Reduced Risk of Distal Colon but Not Overall Colorectal Cancer

Matthew Stenger  / February 15, 2014

In a study reported in Journal of the National Cancer Institute, Kyrø and colleagues found that high levels of plasma alkylresorcinols, biomarkers of dietary whole-grain wheat and rye intake, were associated with reduced risk of distal colon cancer. The study involved prediagnostic plasma samples f...

Multiple Myeloma

Phospho-cMET Inhibition in Multiple Myeloma

Matthew Stenger  / December 1, 2013

In a study reported in Clinical Cancer Research, Moschetta and colleagues characterized the involvement of the cMet oncogene in drug resistance and the activity of a novel selective inhibitor of cMET/phospho-cMET (SU11274) in multiple myeloma cells sensitive (RPMI-8226 and MM.1S) and resistant (R5 a...

CNS Cancers
Head and Neck Cancer

Tumor-Infiltrating Lymphocytes in Glioblastoma Are Related to Specific Genomic Alterations

Matthew Stenger  / November 15, 2013

The role of tumor-infiltrating lymphocytes in glioblastoma has not been fully defined. In a study reported in Clinical Cancer Research, Rutledge and colleagues assessed the association between tumor-infiltrating lymphocytes and molecular alterations, histologies, and survival in glioblastoma. In th...

Pancreatic Cancer

Fatty Acid Network Exerts Growth Inhibitory Effects in Pancreatic Cancer

Matthew Stenger  / November 15, 2013

In a study reported in Clinical Cancer Research, Zhang and colleagues used integrated metabolomics and transcriptomics to investigate gene-metabolic networks and identify metabolic pathways that are perturbed in pancreatic ductal adenocarcinoma.  A global metabolite profiling analysis was performed...

Gynecologic Cancers

Focal Adhesion Kinase Regulates YB-1–Mediated Paclitaxel Resistance in Ovarian Cancer

Matthew Stenger  / November 15, 2013

It has been found that focal adhesion kinase (FAK) inhibition sensitizes ovarian cancer to the effects of taxanes. In a study reported in the Journal of the National Cancer Institute, Kang and colleagues evaluated the response of taxane-resistant and taxane-sensitive ovarian cancer models to a novel...

Skin Cancer

Cytokine-Induced Killer Cells Effective Against Autologous Metastatic Melanoma Including Cells With Stemness Features 

Matthew Stenger  / September 15, 2013

In a study reported in Clinical Cancer Research, Gammaitoni and colleagues investigated the tumor-killing activity of cytokine-induced killer cells against autologous metastatic melanoma and putative cancer stem cells. The investigators developed a preclinical autologous model using same patient-ge...

CNS Cancers

Resistance to Anti-VEGF Drugs in Glioblastoma Is Linked to Mesenchymal Transition 

Matthew Stenger  / September 15, 2013

Antiangiogenic therapy reduces tumor vascular permeability and delays tumor progression but may ultimately promote an aggressive treatment-resistant phenotype. In a study reported in Clinical Cancer Research, Piao and colleagues attempted to identify factors responsible for glioblastoma resistance t...

Gastrointestinal Cancer

Prognostic Significance of MTOR Pathway Component Expression in Neuroendocrine Tumors 

Matthew Stenger  / September 15, 2013

The MTOR serine/threonine kinase pathway is implicated in regulation of neuroendocrine tumor growth. In a study reported in the Journal of Clinical Oncology, Qian and colleagues investigated the potential prognostic significance of MTOR pathway component expression in patients with neuroendocrine tu...

Colorectal Cancer

Treating BRAF V600E Colorectal Cancer May Require Concomitant BRAF and PI3K/mTOR Inhibition 

Matthew Stenger  / July 10, 2013

BRAF V600E mutations are associated with poor prognosis in colorectal cancer. A study by Coffee and colleagues examined PI3K/mTOR signaling in BRAF V600E colorectal cancer cell lines after BRAF inhibition as well as cell viability and apoptosis after combined BRAF and PI3K/mTOR inhibition.  Western...

Breast Cancer

Effect of Radium-223 Dichloride in Breast Cancer Bone Metastasis Model 

Matthew Stenger  / July 10, 2013

Radium-223 dichloride (Xofigo) is an alpha particle–emitting radiotherapeutic drug that mimics calcium and localizes to areas of high bone turnover, providing targeted therapy for skeletal metastasis. The drug was recently approved for treatment of patients with castration-resistant prostate cancer,...

Lung Cancer

Circulating Tumor Cells with ALK Rearrangement in ALK-positive NSCLC 

Matthew Stenger  / June 25, 2013

The diagnostic test for ALK rearrangement in non–small cell lung cancer (NSCLC) for crizotinib (Xalkori) treatment currently uses biopsy or fine-needle aspiration. Pailler and colleagues assessed whether ALK rearrangement could be detected using circulating tumor cells. They analyzed circulating tum...

Pancreatic Cancer

Elevated Serum miR-1290 May Distinguish Early Pancreatic Cancer  

Matthew Stenger  / June 25, 2013

In studies to identify circulating microRNA levels that could distinguish low-stage pancreatic cancer from healthy and disease controls, Li and colleagues, measured 735 microRNAs in pancreatic cancer case and control sera and selected 18 microRNA candidates for validation in an independent set of ca...

Colorectal Cancer

Serum miR-21 as Diagnostic and Prognostic Biomarker in Colorectal Cancer 

Matthew Stenger  / June 25, 2013

The oncogenic microRNAs miR-21and miR-31 negatively regulate tumor-suppressor genes. Toiyama and colleagues conducted a series of studies to assess their potential as serum biomarkers in colorectal cancer. Screening in medium from two colorectal cancer cell lines and serum analysis in 12 patients w...

Lung Cancer

Synergy of Metformin and Gefitinib in LKB1 Wild-type NSCLC Cell Lines 

Matthew Stenger  / June 25, 2013

Clinical resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor treatment has been observed in lung cancer. The antidiabetic drug metformin has shown significant inhibitory and proapoptotic effects in several cancer models alone and in combination with chemotherapeutic drugs...

Breast Cancer

Epigenome-wide Study of DNA Methylation in Breast Cancer Using Prospectively Collected Samples 

Matthew Stenger  / June 25, 2013

Available data suggest that DNA methylation in blood is a potential epigenetic marker of cancer risk, but this has not been evaluated on a genome-wide scale in prospective studies of breast cancer. Xu and colleagues measured DNA methylation at 27,578 CpG sites (ie, DNA regions where cytosine and gua...

Leukemia

New Susceptibility Variants for Childhood ALL in Ethnically Diverse Populations 

Matthew Stenger  / June 25, 2013

Acute lymphoblastic leukemia (ALL) is the most common cancer in children, and the incidence of the disease varies by ethnicity. Available evidence indicates an inherited predisposition to ALL, but the genetic basis of ALL susceptibility in diverse ancestry has not been examined in detail. Xu and col...

Multiple Myeloma

Control of Autophagic Cell Death by Caspase-10 in Multiple Myeloma

Matthew Stenger  / May 15, 2013

Multiple myeloma subtypes are driven by a variety of genetic abnormalities. Given the genetic diversity of the disease, identification of oncogenic mechanisms common to all subtypes is highly desirable. In a study reported in Cancer Cell, Lamy and colleagues found that that all multiple myeloma line...

C-Reactive Protein Downregulates TRAIL, a Cytokine with Key Role in Cancer Immune Surveillance 

Matthew Stenger  / May 15, 2013

C-reactive protein is a biomarker of acute and chronic inflammation that is frequently elevated in patients with cancer. In a study reported in Clinical Cancer Research, Secchiero and colleagues found that increased levels of C-reactive protein were associated with downregulation of TRAIL, a cytokin...

Breast Cancer

Epithelial-to-mesenchymal Transition and Autophagy Induction in Breast Carcinoma Promote Escape from T-cell–mediated Lysis

Matthew Stenger  / May 15, 2013

Epithelial-to-mesenchymal transition is known to mediate cancer cell invasion, metastasis, and drug resistance, but its impact on cancer immune surveillance is less well defined. In a study reported in Cancer Research, Akalay and colleagues found that epithelial-to-mesenchymal transition and autopha...

Lung Cancer

HDAC Inhibition Circumvents EGFR Tyrosine Kinase Inhibitor Resistance Due to BIM Polymorphism 

Matthew Stenger  / May 15, 2013

Upregulation of BIM (BCL2L11), a proapoptotic member of the BCL2 protein family, is required for induction of apoptosis by EGFR tyrosine kinase inhibitors in EGFR-mutant forms of non–small cell lung cancer (NSCLC). A BIM deletion polymorphism occurs naturally in approximately 13% of East Asian indiv...

Breast Cancer

Common Deletion in APOBEC3 Genes Associated with Increased Risk of Breast Cancer 

Matthew Stenger  / May 15, 2013

Genome-wide association studies have identified numerous genetic susceptibility loci for breast cancer, although these loci explain only a small proportion of heritability. Relatively few studies have assessed associations of breast cancer risk with copy number variation, another important source of...

Solid Tumors

p53 Inactivation in the Tumor Microenvironment Promotes Tumor Progression via Immunosuppressive Lymphoid-like Stromal Network

Matthew Stenger  / April 15, 2013

Inactivation of the tumor suppressor p53 through somatic mutations is observed in approximately half of cancers. The finding that p53 mutations sometimes occur in tumor-associated fibroblasts and are correlated with an increased rate of metastases and poor prognosis suggests that p53 dysfunction in ...

Pancreatic Cancer

Effects of siRNA Combining TGF-β1 Silencing and RIG-I Activation in Pancreas Cancer 

Matthew Stenger  / April 15, 2013

Dysregulation of TGF-β signaling promotes tumor growth, invasion, metastasis, and a potent immunosuppressive network in pancreas cancer. A strategy for disrupting the tumor-promoting pathway is the silencing of TGF-β by use of small-interfering (si) RNA. Ellermeier and colleagues found that the intr...

Colorectal Cancer

Mixed-lineage Kinase 4 Interacts with Activated RAS Signaling in Colorectal Cancer

Matthew Stenger  / April 15, 2013

Colorectal cancer that is microsatellite stable but chromosomally unstable is characterized by poor prognosis and remains largely intractable at the metastatic stage. Mutational analysis has shown that the mixed lineage kinase 4 (MLK4) protein kinase is frequently mutated in microsatellite-stable co...

Kidney Cancer

Three-marker Assay for Early Detection of Renal Cancer

Matthew Stenger  / April 15, 2013

Early detection of renal cell carcinoma using biomarkers remains challenging. Kim and colleagues recently evaluated a three-marker assay consisting of nicotinamide N-methyltransferase (NNMT), L-plastin (LCP1), and nonmetastatic cells 1 protein (NM23A). After validation of the three-marker assay in ...

Skin Cancer

Vemurafenib-resistant BRAF-mutant Melanoma

The ASCO Post  / March 1, 2013

Mutational activation of BRAF is the most prevalent genetic alteration in melanoma, with ≥ 50% of tumors expressing the BRAF(V600E) oncoprotein. Vemurafenib (Zelboraf) produces tumor regression and improved survival in patients with late-stage BRAF-mutated melanoma. However, most patients relapse wi...

Colorectal Cancer

Genetic and Epigenetic Alterations in Colorectal Cancer and Metastases

The ASCO Post  / March 1, 2013

Treatment of colorectal cancer is complicated by the potential difference in molecular profiles between the primary tumor and metastases. Miranda and colleagues from the Humanitas Clinical and Research Center in Milan, Italy, recently assessed the presence of molecular heterogeneity during metastati...

Prostate Cancer
Issues in Oncology

Role of Glutamate and Effect of Its Blockade in Prostate Cancer

Matthew Stenger  / December 15, 2012

Glutamate plays a role in oncogenic metabolic and signaling pathways. In a recently reported study, Koochekpour and colleagues from the Roswell Park Cancer Institute in Buffalo, NY, investigated potential correlations of glutamate levels with prostate cancer in patients with primary or castrate-resi...

Breast Cancer

HIV Protease Inhibitor Nelfinavir Selectively Inhibits HER2-positive Breast Cancer Cells

Matthew Stenger  / November 15, 2012

Shim and colleagues from Johns Hopkins School of Medicine in Baltimore, the National Cancer Institute in Bethesda, and Emory University School of Medicine in Atlanta have recently shown that the HIV protease inhibitor nelfinavir (Viracept) is a selective inhibitor of HER2-positive breast cancer cell...

Breast Cancer

Mutational Activation of PI3K-AKT Pathway and Change in HER2 Expression in Trastuzumab-resistant Breast Cancer

Matthew Stenger  / November 15, 2012

Insensitivity of HER2-amplified breast cancer to trastuzumab (Herceptin) has been associated with both changes in HER2 expression and activation of the PI3K-AKT pathway in laboratory studies. Chandarlapaty and colleagues from Memorial- Sloan Kettering Cancer Center in New York and Fox Chase Cancer C...

Impaired Plasmacytoid Dendritic Cell IFN-α Production May Contribute to Breast Cancer Progression

Matthew Stenger  / November 15, 2012

Infiltration and dysfunction of immune cells has been observed in numerous cancers. After finding that plasmacytoid dendritic cells (pDC) in primary breast tumors correlated with unfavorable prognosis, Sisirak and colleagues from INSERM (Institut National de la Santé et de la Recherche Médicale) and...

Issues in Oncology

Noninvasive Measurement of Interstitial Fluid Pressure as Marker of Tumor Aggressiveness

Matthew Stenger  / November 1, 2012

Increased interstitial fluid pressure in tumors can cause metastatic dissemination and treatment resistance. Study of interstitial fluid pressure has been challenging due to a lack of noninvasive imaging strategies. In a recent study, Hompland and colleagues from the Institute of Cancer Research at ...

Issues in Oncology

Whole-blood RNA Expression Profiles as Prognostic Models for Castration-resistant Prostate Cancer

Matthew Stenger  / November 1, 2012

Survival among patients with castration-resistant prostate cancer is highly variable, and there is a scarcity of prognostic markers that could be used to stratify patients in clinical trials, improve treatment, and accelerate drug development. Two recent studies reported in Lancet Oncology have show...

Issues in Oncology

Genome-wide Analysis Reveals Molecular Pathway Aberrations in Uterine Serous Cancer

Matthew Stenger  / November 1, 2012

The molecular pathogenesis of uterine serous carcinoma, the most aggressive form of uterine cancer, remains largely undefined. Kuhn and colleagues from Johns Hopkins Medical Institutions recently identified prominent genetic alterations in uterine serous carcinoma using whole-exome sequencing. Soma...

Predictive Markers for Outcome with Pazopanib in Metastatic Renal Cell Cancer

Matthew Stenger  / September 15, 2012

Several targeted drugs are approved for treatment of metastatic renal cell cancer, but no validated biomarkers are available for prediction of clinical outcome of treatment with these agents. In a recent study, Tran and colleagues from The University of Texas MD Anderson Cancer Center in Houston, Gl...

Metastasis Promoted by Cleaving and Inhibiting Proapoptotic Effect of von Willebrand Factor

Matthew Stenger  / September 15, 2012

Mochizuki and colleagues from Keio University in Tokyo, the Chemo-Sero-Therapeutic Research Institute in Kumamoto, and RIKEN in Saitama have shown that von Willebrand factor has proapoptotic effects and that a disintegrin and metalloproteinase 28 (ADAM28) promotes metastasis by cleaving and inactiva...

Evolutionary Pathways in BRCA1-associated Breast Tumors

Matthew Stenger  / September 15, 2012

BRCA1 germline mutations are associated with elevated risk of breast and ovarian cancers, and somatic loss of the wild-type BRCA1 allele has been thought to be a rate-limiting initiating step in tumor development. BRCA1-associated breast tumors acquire additional somatic alterations during progressi...

VEGF Pathway Biomarker for Outcome with Bevacizumab

Matthew Stenger  / September 15, 2012

No biomarkers are available to guide patient selection for treatment with the anti-VEGF monoclonal antibody bevacizumab (Avastin). Lambrechts and colleagues from VIB and KULeuven and University Hospital Gasthuisberg, Belgium, and F. Hoffmann-La Roche in Basel, Switzerland, have identified a locus in...

TRIM27 as Target in Cancer Development

Matthew Stenger  / September 15, 2012

The tripartite motif family protein 27 (TRIM27) is a transcriptional repressor that reduces induction of cell senescence by retinoblastoma-associated protein (RB1). High levels of TRIM27 expression occur in several human cancers and have been associated with poor prognosis in breast and endometrial ...

Prostate Cancer

Pretreatment Tumor Hypoxia Predicts Biochemical Failure after Radiotherapy for Prostate Cancer

Matthew Stenger  / July 15, 2012

Hypoxia often occurs early in solid tumor development as a result of imbalances between oxygen supply and consumption and may lead to genetic and molecular signaling that influences the biology and clinical behavior of tumors and response to treatment. Milosevic and colleagues from Princess Margaret...

Prostate Cancer

Pretreatment Tumor Hypoxia Predicts Biochemical Failure after Radiotherapy for Prostate Cancer

Matthew Stenger  / June 15, 2012

Hypoxia often occurs early in solid tumor development as a result of imbalances between oxygen supply and consumption and may lead to genetic and molecular signaling that influences the biology and clinical behavior of tumors and response to treatment. Milosevic and colleagues from Princess Margaret...

Issues in Oncology

Complex Relationship between Metformin and BRAF-mutant Tumors

Matthew Stenger  / June 15, 2012

The antidiabetic drug metformin appears to lower cancer risk in diabetic patients and has shown antitumor activity in preclinical studies. Suppression of mTOR signaling via AMP kinase (AMPK)-dependent TOR complex 1 (TORC1) inhibition is one of the proposed mechanisms by which metformin appears to su...

Gynecologic Cancers
Issues in Oncology

Gab2 Promotes Characteristics of Epithelial-to-Mesenchymal Transition in Ovarian Cancer

Matthew Stenger  / June 15, 2012

Ovarian cancer is often diagnosed at a late stage, when cancer cells have already migrated and invaded other tissues and organs. Wang and colleagues from the University of Colorado Denver and the Dana-Farber Cancer Institute in Boston, showed that Gab2—a scaffolding adaptor protein that is overexpre...

Pancreatic Cancer

Anti-EpCAM Antibody-Drug Conjugate Shows High Activity against Pancreatic Cancer

Matthew Stenger  / June 15, 2012

Human epithelial cell adhesion molecule (EpCAM) is overexpressed in many cancers. Although anti-EpCAM antibodies have shown promise in preclinical studies, early-phase clinical evaluation of these antibodies has been disappointing. To determine whether the antitumor activity of anti-EpCAM antibody ...

Breast Cancer

Characteristics of Field Cancerization in Histologically Normal Tissue Adjacent to Breast Tumors

Matthew Stenger  / May 15, 2012

It has been shown that a field of genetically altered but histologically normal tissue extends 1 cm or more from the margins of human breast tumors. The characteristics of this field are not fully understood, although it is clear that the molecular alterations in affected cells could provide mechani...

Colorectal Cancer

Inhibition of IL-8 Receptor Reduces Colorectal Cancer Proliferation and Sensitizes the Disease to Oxaliplatin

Matthew Stenger  / May 15, 2012

Recent studies have shown that interleukin-8 (IL-8) and its receptors CXCR1 and CXCR2 are significantly upregulated in colorectal cancer tumors and their microenvironment and act as regulators of proliferation, angiogenesis, and metastasis. Ning and colleagues from the University of Southern Califor...

Breast Cancer

PEDF Has Cytotoxic Effect on Breast Cancer Cells and Neuron-protective Effect

Matthew Stenger  / May 1, 2012

The cytokine pigment epithelium–derived factor (PEDF) is downregulated in brain metastases of breast cancer by approximately 14-fold compared with primary breast tumors, suggesting that promoting its expression might inhibit metastatic spread. Normal breast epithelial cells express high levels of PE...

Breast Cancer

Targeting Human Endogenous Retrovirus K Envelope Protein Inhibits Breast Cancer Growth

Matthew Stenger  / May 1, 2012

The human genome contains a large variety of endogenous retroviral sequences (approximately 8% of the genome). Although most of these are highly defective, the human endogenous retrovirus type K (HERV-K) family shows conservation of apparently intact retroviral genes and is transcriptionally active ...

Hepatobiliary Cancer

Bone Morphogenesis Protein 4 Pathway as Treatment Target in Hepatocellular Carcinoma

Matthew Stenger  / May 1, 2012

Bone morphogenesis protein 4 (BMP4), which belongs to the transforming growth factor (TGF)-β family, is a multifunctional cytokine that is known to be involved in human carcinogenesis. The cytokine exerts its effects through pathways dependent on and independent of SMAD proteins, which are the intra...

SMAC Mimetics Induce Proinflammatory Cancer Cell Death and Adaptive Antitumor Immune Response

Matthew Stenger  / May 1, 2012

SMAC/DIABLO (second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI) is a proapoptotic mitochondrial protein that is released in response to various apoptotic stimuli. Molecular mimetics of SMAC are being investigated for use in cancer treatment, b...

Issues in Oncology

Targeted Massively Parallel Sequencing Identifies Clinically Relevant Alterations in Cancer Genes

Matthew Stenger  / April 15, 2012

Systematic methods for profiling tumor genomic alterations remain underdeveloped, with current clinical profiling usually being confined to identification of limited numbers of oncogene point mutations. At present, there is no systematic technique for interrogating tumor samples in situ for a compre...

Targeted Mutations in ATR Pathway and Implications for Combination Strategies

Matthew Stenger  / April 15, 2012

Many chemotherapy agents work by causing DNA strand breaks or accumulation of DNA replication intermediates. ATR (ataxia-telangiectasia mutated and Rad 3-related protein) is a potential target for combination drug strategies, because signaling of this protein in response to such altered DNA structur...

Prostate Cancer

Androgen Deprivation Therapy May Lead to Castration Resistance in Prostate Cancer

Matthew Stenger  / April 15, 2012

Although androgen-deprivation therapy is effective in inducing regression of androgen-dependent prostate cancer, relapse often occurs in an androgen-independent manner and is associated with poor prognosis. The mechanisms underlying castration resistance are not fully understood. Sung and colleagues...

Solid Tumors

PI3K Inhibitors May Improve Response to Cancer Immunotherapy

Matthew Stenger  / March 1, 2012

The induction of antitumor immunity by vaccines or immunotherapies is inhibited by the immunosuppressive microenvironment of tumors. Toll-like receptor (TLR) agonists have the potential to increase inflammatory antitumor effects in the microenvironment, but these ligands can exert a mixture of both ...

Colorectal Cancer

Significant Differences in Genetic Characteristics of Primary Colorectal Cancer and Hepatic Metastases

Matthew Stenger  / March 1, 2012

Vermaat and colleagues from the University Medical Center Utrecht, Hubrecht Institute, Utrecht, The Netherlands, and Hoffman-La-Roche Inc./Genentech, Nutley, New Jersey, recently showed that there was significant genetic variation between individual primary colorectal cancer tumors and their subsequ...

Breast Cancer

Six1-Eya2 Interaction a Potential Target in Blocking Breast Cancer Metastasis

Matthew Stenger  / March 1, 2012

The Six1 gene is a key regulator of embryonic development that requires interaction with the Eya family of proteins (Eya1-4) to activate transcription of genes involved in neurogenesis, myogenesis, and nephrogenesis. Overexpression of Six1 and Eya is observed in a number of cancers. In breast cancer...

CNS Cancers

Combination of Oncolytic Virus and Chemotherapy Holds Promise in Glioblastoma

Matthew Stenger  / March 1, 2012

Glioblastoma remains a uniformly lethal disease. Both the alkylating agent temozolomide and oncolytic viruses (engineered to preferentially infect and kill cancer cells) hold promise in treatment of glioblastoma. The effects of combining the two and the mechanisms of their interaction on cancer stem...

Solid Tumors

Targeting AKT/mTOR May Improve Response to Monoclonal Antibodies in Some Cancers

Matthew Stenger  / February 15, 2012

The insulin-like growth factor (IGF) network plays a central role in regulating tumor cell growth and differentiation, tumor angiogenesis, metastasis, apoptosis, and multidrug resistance. Increased IGF-1 receptor (IGF-1R) expression and circulating IGF-1 are associated with increased risk for develo...

Impact of p53 Status on Cancer Treatment Selection

Matthew Stenger  / February 15, 2012

Wild-type p53 emerges from a latent state and becomes stabilized and activated in response to genotoxic and cellular stress signals, resulting in the transcriptional modulation of multiple genes involved in regulating cell-cycle progression, senescence, and apoptosis. More than 50% of human tumors c...

Breast Cancer

Overexpression of p16 Does Not Indicate Increased Risk of Breast Cancer in Women with Atypical Hyperplasia

Matthew Stenger  / February 15, 2012

Women diagnosed with atypical hyperplasia have a substantial risk of subsequent development of breast cancer, with a cumulative incidence of approximately 30% at 25 years. Atypical hyperplasia is considered to be a precursor to ductal carcinoma in situ (DCIS). p16 (a nuclear protein encoded by the p...

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