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Showing 6151 - 6200DNA Repair Pathway Recombination Proficiency Score Correlates With Tumor Sensitivity to Chemotherapy
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...
Epigenetic Reprogramming of HOXC10 Results in Endocrine Resistance in Breast Cancer
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...
IL-17A Promotes and GM-CSF Suppresses Circulating Tumor Cells and Metastasis in Colorectal Cancer
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...
IL-15 Deletion Linked to Reduced Local Proliferation of B and T Cells and Poorer Outcome in Colorectal Cancer
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...
Inactivation of E3 Ubiquitin Ligase Cbl-b Allows Natural Killer Cells to Control Metastases
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...
PPAR-δ/β Overexpression Increases Colon Tumorigenesis
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...
Ramucirumab for Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma
On April 21, 2014, ramucirumab (Cyramza) was approved for use as a single agent in the treatment of patients with advanced or metastatic gastric or gastroesophageal junction adenocarcinoma with disease progression on or after prior treatment with fluoropyrimidine- or platinum-containing...
Ofatumumab Plus Chlorambucil for Previously Untreated CLL in Patients Not Treatable With Fludarabine-Based Regimens
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 April 17, 2014, ofatumumab (Arzerra) received regular approval...
Increased Incidence of Thyroid Cancer: An Epidemic of Diagnosis?
In a study reported in JAMA Otolaryngology Head & Neck Surgery,1 Davies and Welch found that the incidence of thyroid cancer has nearly tripled since 1975. However, the increase appears to represent an “epidemic of diagnosis” and to almost exclusively represent increased diagnosis of papillary...
ASCO Committee Defines Clinically Meaningful Goals for Clinical Trials in Pancreas, Breast, Lung, and Colorectal Cancers
The ASCO Cancer Research Committee recently convened four disease-specific working groups—in pancreas, breast, lung, and colon cancers—to “consider the design of future clinical trials that would produce results that are clinically meaningful to patients.” An ASCO perspective statement, reported in ...
Neoadjuvant Chemotherapy Without Routine Radiotherapy Shows Promise in Patients With Locally Advanced Rectal Cancer
In a pilot study reported in the Journal of Clinical Oncology, Deborah Schrag, MD, MPH, and colleagues from Memorial Sloan Kettering Cancer Center, New York, assessed outcomes with neoadjuvant FOLFOX (fluorouracil, leucovorin, oxaliplatin)/bevacizumab (Avastin) with selective use of...
Continued Survival Benefits Seen With Radical Prostatectomy vs Watchful Waiting in Long-Term Follow-up of the SPCG-4 Trial
The long-term benefits of radical prostatectomy vs watchful waiting in men with localized prostate cancer has remained a debated issue. As reported in The New England Journal of Medicine by Anna Bill-Axelson, MD, of Uppsala University Hospital, and colleagues, additional long-term follow-up in the...
Phase III Study Explores Addition of Nintedanib to Docetaxel in Second-Line Treatment of Non–Small Cell Lung Cancer
In a phase III trial (LUME-Lung 1) reported in The Lancet Oncology, Reck et al assessed the addition of nintedanib to docetaxel in second-line treatment of non–small cell lung cancer (NSCLC).1 The combination significantly improved progression-free survival in all patients and improved overall...
Ceritinib Highly Active in Patients With ALK-Rearranged Advanced NSCLC
Non-small cell lung cancer (NSCLC) harboring ALK rearrangement is sensitive to the ALK inhibitor crizotinib (Xalkori), but resistance ultimately occurs. In a phase I study reported in The New England Journal of Medicine, Alice T. Shaw, MD, PhD, of Dana-Farber/Harvard Cancer Center, Boston, and...
ASCO Releases Adapted Guideline on Screening, Assessment, and Management of Fatigue in Adult Survivors of Cancer
A majority of cancer patients experience some level of fatigue during the course of their treatment, and approximately 30% contend with persistent fatigue for years after treatment. Fatigue is among the most common and distressing long-term effects of cancer treatment and significantly affects...
ASCO Releases Adapted Guideline on Screening, Assessment, and Care of Anxiety and Depressive Symptoms in Adults With Cancer
Detection of depression is suboptimal, and its severity is underestimated in the general population, but it is known psychiatric disorders are more common in patients with cancer than in those with any other chronic illness. Although studies in cancer patients have yielded varying figures, it is...
ASCO Releases Guideline on Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers
ASCO has released a clinical practice guideline on prevention and treatment of chemotherapy-induced peripheral neuropathy in adult cancer patients, published in the Journal of Clinical Oncology.1 The guidelines resulted from the efforts of an expert panel, with representation from the fields of...
High Macrophage Inhibitory Cytokine-1 Levels and Colorectal Cancer Risk
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...
Druggable Oncogene Fusions Found in KRAS Wild-Type Lung Invasive Mucinous Adenocarcinoma
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,...
MTH1 Inhibition Blocks Sanitation of Deoxyribonucleotide Triphosphate Pool and Causes Cancer Cell Death
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...
Copper Chelation for BRAF-Mutated Disease?
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...
ASCO Endorses SSO/ASTRO Guideline on Margins for Breast-Conserving Surgery With Whole-Breast Irradiation in Stage I/II Breast Cancer
As reported in the Journal of Clinical Oncology,1 ASCO has endorsed the recently published Society of Surgical Oncology (SSO) and American Society for Radiation Oncology (ASTRO) consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in stage I and II invasive...
Ceritinib in ALK-Positive Metastatic NSCLC Patients With Progression on or Intolerance to Crizotinib
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 April 29, 2014, ceritinib (Zykadia) was granted accelerated...
Postmastectomy Radiotherapy Reduces Breast Cancer Recurrence and Mortality in Women With One to Three Positive Nodes
Meta-analyses have shown that postmastectomy radiotherapy reduces risks of recurrence and breast cancer mortality in the population of all women with node-positive disease, but outcomes in those with only one to three positive nodes have not been specifically examined. As reported by Paul McGale,...
ASCO Clinical Practice Guideline Update: Sentinel Lymph Node Biopsy for Patients With Early-Stage Breast Cancer
ASCO recently convened an update committee of experts in medical oncology, pathology, radiation oncology, surgical oncology, guideline implementation, and advocacy to develop evidence-based recommendations that update the ASCO 2005 clinical practice guideline on use of sentinel node biopsy in...
Mercaptopurine Oral Suspension for Acute Lymphoblastic Leukemia
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 April 28, 2014, an oral suspension of mercaptopurine (Purixan) ...
Aflibercept More Active Than Bevacizumab in Patient-Derived Colorectal Cancer Xenografts
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...
Physician Attitudes About Multiplex Tumor Genomic Testing: Variation in Projected Use and Confidence
It is a widely expressed belief that predictive multiplex somatic genomic testing represents the ability to transform cancer care by identifying targetable alterations in multiple cancer genes. Do oncologists share this belief? How do they intend to use such tests in practice? In a study reported...
Colonoscopy Adenoma Detection Rate Inversely Proportional to Risk of Interval Colorectal Cancer and Colorectal Cancer Mortality
In a study of health-care organization data reported in The New England Journal of Medicine, Douglas A. Corley, MD, PhD, of Kaiser Permanente, and colleagues assessed the relationship between proportion of colonoscopies performed by a gastroenterologist that detect an adenoma and risk of subsequent ...
ASCO Clinical Practice Guideline: Systemic Therapy for Patients With Advanced HER2-Positive Breast Cancer
Approximately 15% of patients with breast cancer have tumors that overexpress the HER2 protein and these patients can benefit from HER2-targeted therapies. The American Society of Clinical Oncology recently released a clinical practice guideline on systemic therapy for patients with advanced...
Siltuximab for Multicentric Castleman’s Disease
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 April 23, 2014, the anti–interleukin (IL)-6 monoclonal antibody...
Lung Cancer Mutation Consortium Finds Oncogenic Drivers in Majority of Metastatic Lung Adenocarcinomas
The Lung Cancer Mutation Consortium (LCMC) was formed to test adenocarcinomas of the lung for 10 oncogenic drivers in order to enable clinicians to select targeted treatments and enroll patients into suitable clinical trials. As recently reported in JAMA by Mark G. Kris, MD, William and Joy Ruane...
Panitumumab Plus FOLFOX for KRAS Wild-Type Metastatic Colorectal 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. Panitumumab (Vectibix) was recently approved by the U.S. Food and...
ASCO Clinical Practice Guideline: Disease Management in Advanced HER2-Positive Breast Cancer With Brain Metastases
As many as half of all patients with metastatic HER2-positive breast cancer develop brain metastases over time. The American Society of Clinical Oncology recently released a clinical practice guideline on disease management for patients with advanced HER2-positive breast cancer and brain...
Ado-Trastuzumab Emtansine Improves Progression-Free Survival vs Physician’s Choice in Advanced HER2-Positive Breast Cancer
There are few treatment options for breast cancer patients with progressive disease after two or more HER2-directed regimens for recurrent or metastatic disease. In the open-label phase III TH3RESA trial reported in The Lancet Oncology by Ian E. Krop, MD, PhD, of the Dana-Farber Cancer Institute,...
Vaccine Targeting Tumor Antigen to Dendritic Cell Receptors Induces Antigen-Specific Immunity
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...
EGFR Activation Increases Cancer Cell ‘Visibility’ for Cytotoxic T Lymphocytes
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...
High Macrophage Inhibitory Cytokine-1 Levels and Colorectal Cancer Risk
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...
MTH1 Inhibition Blocks Sanitation of Deoxyribonucleotide Triphosphate Pool and Causes Cancer Cell Death
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...
Belinostat for Relapsed/Refractory Peripheral T-Cell Lymphoma
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 July 3, 2014, belinostat (Beleodaq) was granted accelerated...
Swiss Medical Board Members Discuss Recommendation to Phase Out Mammography Screening
In a New England Journal of Medicine “Perspective” article, Nikola Biller-Andorno, MD, PhD, of the University of Zurich and Harvard Medical School, and Peter Jüni, MD, of the University of Bern, provide the rationale for a recent report by the Swiss Medical Board advocating the phasing out of...
Rilotumumab Added to First-Line Chemotherapy May Benefit Patients With Advanced Gastric or Esophagogastric Junction Adenocarcinoma
Hepatocyte growth factor (HGF) and its receptor MET have been found to promote the proliferation, migration, and survival of tumor cells and to play a role in gastric cancer. In a phase II study reported in The Lancet Oncology, Timothy Iveson, MD, of the University Hospital Southampton NHS...
Sorafenib Improves Progression-Free Survival in Progressive Radioactive Iodine–Refractory Differentiated Thyroid Cancer
Patients with radioactive iodine–refractory locally advanced or metastatic differentiated thyroid cancer have a poor prognosis. In the double-blind phase III DECISION trial reported in The Lancet, Marcia S. Brose, MD, PhD, of Abramson Cancer Center of the University of Pennsylvania, and colleagues ...
Centrosome Amplification Promotes Cellular Invasion in Mammary Epithelial Cells
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...
IGF-2/IGF-1R Inhibition Shows Promise in Esophageal Cancer
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....
Plasma Tumor DNA Detectable Before and After Surgery in Patients with Early-Stage Breast Cancer
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...
Melanoma Metastases Exhibit Site-Specific Antigen Heterogeneity Correlating With T-Cell Infiltration
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...
Mutations in IGF Pathway Genes Associated With Prostate Cancer Mortality
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...
Mesenchymal Stem Cells With Oncolytic HSV Variants Promising in Glioblastoma Multiforme
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...
FBXW7 as Tumor Suppressor and NOTCH1 Inhibition as Potential Strategy in Melanoma
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 ...
