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gynecologic cancers

Bevacizumab in Persistent, Recurrent, or Metastatic Cervical Cancer

In the Clinic provides overviews of novel oncology agents, addressing indications, mechanisms, administration recommendations, safety profiles, and other essential information needed for the appropriate clinical use of these drugs.   On August 14, 2014, bevacizumab (Avastin) was approved for the...

multiple myeloma

Bortezomib Retreatment in Multiple Myeloma

In the Clinic provides overviews of novel oncology agents, addressing indications, mechanisms, administration recommendations, safety profiles, and other essential information needed for the appropriate clinical use of these drugs. On August 8, 2014, the approved use of bortezomib (Velcade) in...

Residents Association Recognizes 57 Mentors and Teachers With 2014 Educator of the Year Award

The Association of Residents in Radiation Oncology (ARRO) has honored 57 educators with the 2014 Educator of the Year Award. The award, presented annually, recognizes outstanding teachers and mentors of radiation oncology residents. Each radiation oncology residency program may nominate one faculty ...

solid tumors

Potential 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...

multiple myeloma

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...

skin cancer

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 ...

colorectal cancer

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...

lung cancer

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 ...

colorectal cancer

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 ...

leukemia

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...

colorectal cancer

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...

issues in oncology

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 ...

breast cancer
gastroesophageal cancer

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...

Expert Point of View: Karla Kerlikowske, MD

In an accompanying editorial,1 Karla Kerlikowske, MD, of the University of California, San Francisco, and colleagues point out that while the finding of Killelea et al that digital mammography screening was not associated with downstaging of disease may not be surprising, given the similar accuracy ...

breast cancer

Study Finds Increased Breast Cancer Screening Costs in Medicare Population but No Increase in Cancer Detection

In a study of the use of breast cancer screening modalities in the Medicare population reported in Journal of the National Cancer Institute, Brigid K. Killelea, MD, MPH, FACS, and colleagues at Yale University School of Medicine, Yale Cancer Center, and Yale–New Haven Hospital, New Haven,...

breast cancer

Adding Tomosynthesis to Digital Mammography Decreased Recall Rate, Increased Cancer Detection Rate in Breast Cancer Screening

In a large multicenter study reported in JAMA, Sarah M. Friedewald, MD, of the Advocate Lutheran General Hospital, Center for Advanced Care, Park Ridge, Illinois, and colleagues found that use of tomosynthesis plus digital mammography reduced the recall rate and increased the cancer detection rate...

bladder cancer

No Difference in Complication Rates or Hospital Stay With  Robot-Assisted vs Open-Surgery Cystectomy in Bladder Cancer

Retrospective analyses indicate that robot-assisted laparoscopic surgery for radical cystectomy in patients with bladder cancer is associated with reduced risk of complications and shorter hospital stay compared with open surgery. In a small single-institution randomized trial reported in a letter...

breast cancer

Study Quantifies Risk of Hereditary Breast Cancer in Carriers of PALB2 Mutations

In a study reported in The New England Journal of Medicine, Antonis C. Antoniou, PhD, Reader in Cancer Risk Prediction and Cancer Research UK Senior Cancer Research Fellow at the University of Cambridge, and colleagues identified lifetime risk of breast cancer in families with germline...

gynecologic cancers

Adding Antiangiopoietin Agent Trebananib to Paclitaxel Improves Progression-Free Survival in Recurrent Epithelial Ovarian Cancer

Trebananib inhibits angiogenesis by blocking the binding of angiopoietins 1 and 2 to the Tie2 receptor expressed on endothelial cells, a mechanism that differs from vascular endothelial growth factor (VEGF) inhibitors and that involves a different signaling pathway. In the phase III TRINOVA-1 trial ...

prostate cancer

European Researchers at 13-Year Follow-up: Increased Absolute Benefit of PSA Screening in Prostate Cancer Mortality, but Time for Population-Based Screening Has Not Arrived

The 13-year follow-up of the European Randomized Study of Screening for Prostate Cancer ­(ERSPC), reported by Fritz H. Schröder, MD, PhD, Professor Emeritus of Urology at Erasmus University Medical Center, Rotterdam, the Netherlands, and colleagues in The Lancet, showed that prostate-specific...

breast cancer

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...

cns cancers

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...

cns cancers

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...

issues in oncology

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...

gastrointestinal cancer

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...

head and neck cancer

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...

breast cancer

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...

prostate cancer

Primary Androgen Deprivation Does Not Improve Long-Term Survival in Older Patients With Localized Prostate Cancer

Primary androgen-deprivation therapy has been widely used in localized prostate cancer, despite the absence of definitive evidence of benefit in early-stage disease. In a large population-based cohort study reported in JAMA Internal Medicine, Grace L. Lu-Yao, MPH, PhD, of Rutgers Cancer Institute...

issues in oncology

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, ...

issues in oncology

The Value of Lifelong Mentorship in Career Development

While the development of mentorship relationships is critical in launching and nurturing the academic careers of young investigators, it is also an essential component for continued success throughout their careers, according to Jennifer R. Brown, MD, PhD. Dr. Brown, Director of the CLL Center at...

prostate cancer

Enzalutamide in Metastatic Castration-Resistant Prostate Cancer

In the Clinic provides overviews of novel oncology agents, addressing indications, mechanisms, administration recommendations, safety profiles, and other essential information needed for the appropriate clinical use of these drugs.   On September 10, 2014, the androgen receptor inhibitor...

supportive care

Integrated Collaborative Care Program Highly Successful in Treating Major Depression in Patients With Cancer

In the Scottish SMaRT Oncology-2 study reported in The Lancet, Michael Sharpe, MD, and Jane Walker, PhD, of University of Oxford, United Kingdom, and colleagues found that an integrated collaborative treatment program for depression (“depression care for people with cancer”) was associated with...

cns cancers

CENTRIC Trial Shows No Benefit of Adding Cilengitide to Therapy in Glioblastoma With Methylated MGMT Promoter

In the phase III CENTRIC/European Organisation for Research and Treatment of Cancer (EORTC) 26071-22072 trial reported in The Lancet ­Oncology, Roger Stupp, MD, of University Hospital Zurich, and colleagues found that adding the selective αvβ3 and αvβ5 integrin inhibitor cilengitide to standard...

lymphoma

Time to Treatment Failure Similar With Rituximab Retreatment vs Maintenance in Low–Tumor Burden Follicular Lymphoma

Maintenance rituximab (Rituxan) has been shown to improve progression-free survival vs observation in low–tumor burden follicular lymphoma. In the Eastern Cooperative Oncology Group (ECOG) E4402 Trial ­(RESORT), reported in the Journal of Clinical Oncology, Brad S. Kahl, MD, of the University of...

colorectal cancer

Lower- vs Higher-Than-Expected Long-Term Colorectal Cancer Mortality After Removal of Lower- vs Higher-Risk Adenomas

Few data are available on long-term risk of colorectal cancer mortality after adenoma removal. In a Norwegian study reported in The New England Journal of Medicine, Magnus Løberg, MD, of the Department of Health Management and Health Economics, University of Oslo, and colleagues found that patients ...

skin cancer

First Approval of PD-1 Inhibitor: Pembrolizumab in Unresectable or Metastatic Melanoma

In the Clinic provides overviews of novel oncology agents, addressing indications, mechanisms, administration recommendations, safety profiles, and other essential information needed for the appropriate clinical use of these drugs.   On September 4, 2014, pembrolizumab (Keytruda) was granted...

breast cancer

ASCO Clinical Practice Guideline: Chemotherapy and Targeted Therapy in Advanced HER2-Negative or HER2 Status–Unknown Breast Cancer

The American Society of Clinical Oncology has released a new clinical practice guideline on chemotherapy and targeted therapy for women with advanced HER2-negative or HER2 status–unknown breast cancer. The guideline is published in the Journal of Clinical Oncology.1 In formulating the consensus...

lung cancer

Significant Improvement in Overall Survival With Second-Line Addition of Ramucirumab to Docetaxel in Stage IV NSCLC

In the phase III REVEL trial reported in Lancet, Edward B. Garon, MD, of the David Geffen School of Medicine at UCLA/Translational Research in Oncology–US Network, Los Angeles, and colleagues found that the addition of the antiangiogenic vascular endothelial growth factor receptor (VEGFR)-2...

colorectal cancer

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...

prostate cancer

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...

hepatobiliary cancer

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...

supportive care

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...

bladder cancer

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...

head and neck cancer

No Benefit Seen for Cetuximab Added to Cisplatin and Accelerated Radiotherapy in Advanced Head and Neck Carcinoma

Use of cisplatin or cetuximab (Erbitux) with radiotherapy improves overall survival in stage III or IV head and neck carcinoma, and adding cetuximab to platinum therapy improves overall survival in metastatic disease. In the phase III Radiation Therapy Oncology Group (RTOG) 0522 trial reported in...

leukemia

Recent Reports and Perspectives on Chronic Lymphocytic Leukemia

Recent articles on developments and controversies in the treatment of chronic lymphocytic leukemia include the following features from The ASCO Post, which are also available at www.ascopost.com: “Recent FDA Approvals Foster Growing Treatment Armamentarium for Chronic Lymphocytic Leukemia and Rare ...

cns cancers

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...

leukemia

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,...

breast cancer

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...

breast cancer

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...

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