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Showing 851 - 900Potential for Therapeutic Autovaccination Against Solid Tumors With Intratumoral Poly-ICLC
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...
Modification of T Cells to Target CS1 Improves Eradication of Myeloma Cells
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...
PD-1 Identifies Patient-Specific CD8-Positive Tumor-Infiltrating Lymphocytes in Melanoma
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 ...
LCS6 Genotype Not Associated With KRAS Mutation Status or Outcome in Stage III Colon Cancer
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...
Remarkable Response to Sorafenib in Advanced Lung Adenocarcinoma and Oncogenic ARAF Mutation
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 ...
Overexpression of Sirt7 Is Associated With Tumorigenesis and Poor Prognosis in Colorectal Cancer
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 ...
Tissue Microenvironment Affects Activity of PTEN in Leukemia
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...
Potential Marker for Response to Anti-EGFR Therapy in KRAS Wild-Type Metastatic Colorectal Cancer
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...
Extracellular Matrix Stiffness Promotes Malignant Progression Via PTEN-Reducing Effect of Micro-RNA
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 ...
TRIM44 Amplification in Esophagogastric, Breast Tumors May Be Marker for mTOR Inhibitor Therapy
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...
Delivering Cancer Care in Low-Income Countries
In eealthy industrialized nations like the United States, escalating costs of cancer care have put the term “cost-effective care” on the forefront of health-care policy discussions. However, the cost issues we wrestle with in our $3 trillion health-care system are vague abstractions for much of the ...
Immunotherapy Research of James P. Allison, PhD, Has Led to a Paradigm Shift in the Treatment of Cancer
James P. Allison, PhD, has been bucking the status quo since he was a teenager growing up in the small agricultural town of Alice, Texas, in the 1950s and 1960s. He first butted heads with authority figures when he was in high school and learned that his biology class had omitted the teaching of...
PALB2 Study: Researchers and Patients Must 'Pal' for Progress
The recent publication by Antoniou et al on risk of breast cancer in PALB2 carriers,1 reviewed in this issue of The ASCO Post (page 47), is a contribution to the interesting history of the PALB2 gene, and an important milestone in the expansion of hereditary cancer susceptibility testing in the...
Different Transcriptional Responses to Fulvestrant and Estrogen Deprivation in ER-Positive Breast Cancer
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...
MSH6 Mutations May Influence Temozolomide Resistance in Treatment-Naive Gliomas Independent of MGMT Methylation
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...
Dissemination of Glioblastoma Multiforme Outside Brain Is Common
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...
Potential for Improved Effectiveness and Reduced Toxicity of Radiotherapy With Ultrahigh Dose-Rate FLASH Irradiation
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...
CD44 Expression a Marker for Chemotherapy Resistance in Gastric Cancer, Overcome by Hedgehog Inhibition
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...
TP53 Mutation Associated With Chromosome 3p Loss in Head and Neck Squamous Cell Carcinoma
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...
Tumor PD-L1 mRNA Expression Associated With Improved Outcome in Breast Cancer
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...
Roswell Park Researchers Awarded Nearly $5 Million to Support Research Projects
Several faculty members at Roswell Park Cancer Institute have been awarded nearly $5 million in grant funding from public and private organizations to further their efforts to find new and better ways to detect and treat cancer and improve patients’ quality of life. The 13 awards, including two for ...
On Being A Mentee and the Value of the Conquer Cancer Foundation’s Career Development Award
At the ASCO Annual Meeting in June, the Conquer Cancer Foundation presented the 2014 recipients of prestigious grants and awards, including the Young Investigator Award, Career Development Award, and the Advanced Clinical Research Award in Breast Cancer. In announcing the awards, Charles W. Penley, ...
Life-Threatening Dermatologic Toxicity
A variety of life-threatening dermatologic adverse events may occur in association with cancer drug therapies. Here, we discuss the recognition and management of three types of such toxicities: type I hypersensitivity/anaphylaxis, Stevens-Johnson syndrome/toxic epidermal necrolysis, and drug rash...
How Accurate Is the Pathologic Assessment of the Partial Mastectomy Specimen?
The pathologic evaluation of lumpectomy margins is “fraught with problems and pitfalls,” said Stuart J. Schnitt, MD, Director of Anatomic Pathology at Beth Israel Deaconess Medical Center and Professor of Pathology at Harvard Medical School, Boston, who was part of a multidisciplinary discussion of ...
Polymorphisms and Cetuximab Benefit in Locally Advanced Rectal Cancer
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...
Androgen, Estrogen, and Stem Cell Markers Help Predict Recurrence and Survival in Metastatic Prostate Cancer
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...
Chemotherapy-Induced Immunosuppressive Myeloid Cells Inhibit Tumor Control via PD-1–PD-L1 Axis
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...
Successful Immunotherapy With Mutation-Specific CD4-Positive T Cells in Patient With Epithelial Cancer
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...
MHC-Matched Graft-vs-Host Disease Requires Recipient Intestinal Barrier Loss and Natural Killer Cell Inactivation
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...
EGFR a Potential Target in Muscle-Invasive Bladder Cancer With Basal-Like Phenotype
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...
NCI Awards $2 Million Grant to University of Pittsburgh School of Dental Medicine to Study How Cancer Spreads to Bone
With a $2 million, 5-year grant from the National Cancer Institute (NCI), researchers at the University of Pittsburgh School of Dental Medicine will examine the molecular mechanisms that allow certain cancers, particularly multiple myeloma, to spread to the bone. The project could lead to new...
Clinical Trials Actively Recruiting Patients With Lung Cancer
The information contained in this Clinical Trials Resource Guide includes actively recruiting clinical studies of people with lung neoplasms, including stage I and II small cell and non–small cell lung cancers. The studies include phase Ib, II, III, observational, and interventional trials...
Effect of Micro-RNA on M2 Macrophages and Murine Glioblastoma
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...
Sonic Hedgehog Factor GLI1 Induces Resistance to Cytarabine and Ribavirin in AML via Glucuronidation
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,...
Suppressor of Cytokine Signaling Protein Promotes Breast Cancer Recurrence by Potentiating c-MET Signaling
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...
DNA Double-Strand Break Repair Genes and Oxidative Damage in Brain Metastasis of Breast Cancer
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...
Peripheral Nerve Schwann Cells Migrate to Pancreas and Colon Cancer Cells Before Invasion
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...
Potential Roles for Metformin and Everolimus in Obese Women With ER-Positive Breast Cancer
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...
RNA-Binding Protein Destabilizes Transcripts of Novel Metastasis Suppressor Genes in Breast Cancer
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...
The Power of Laughter
The following essay by Julie Vose, MD, MBA, FASCO, is adapted from The Big Casino: America’s Best Cancer Doctors Share Their Most Powerful Stories (May 2014), coedited by Stan Winokur, MD, and Vincent Coppola. The book is available on Amazon.com and thebigcasino.org. When I met Cindy, she was...
Overutilization a Key Target in Efforts to Control Health-Care Costs
Overutilization of health-care interventions has become a prime target of efforts to rein in health-care costs. Overtreatment of cancer patients is associated with a number of common harms to the patient—not just financial harm to the health-care system. At the recent ASCO Quality Care Symposium in ...
mTOR Cotargeting Active in Cetuximab-Resistant Head/Neck Cancers With PIK3CA and RAS Mutations
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...
Single-Nucleus Genome Sequencing Shows Early Aneuploid Rearrangement and Gradual Clonal Evolution in Breast Cancer
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....
Hyperthermia Reduces Gemcitabine Resistance
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...
PRC2 Loss Amplifies RAS-Driven Transcription and Results in Sensitivity to Bromodomain Inhibition
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...
Selective Generation of Reactive Oxygen Species in Tumor Cells
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...
Mitochondrial Respiration as Target in KRAS-Mutant Pancreatic Cancer
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...
Antitumor Effect of Intratumoral Injection of Clostridium Spores
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 ...
Memorial Sloan Kettering Team Discovery Advances Understanding of Immunotherapy’s Successes—and Its Failures
A collaborative team of leaders in the field of cancer immunology from Memorial Sloan Kettering Cancer Center has made a key discovery that advances the understanding of why some patients respond to the CTLA-4 blocking antibody ipilimumab (Yervoy), an immunotherapy drug, while others do not. A...
CD19-Directed CAR T Cells Produce Sustained Remission in Relapsed/Refractory Acute Lymphoblastic Leukemia
In a study reported in The New England Journal of Medicine, Shannon L. Maude, MD, PhD, of Children’s Hospital of Philadelphia, and Noelle Frey, MD, of the Perelman School of Medicine, University of Pennsylvania, and colleagues reported achieving sustained remissions in children and adults with...
