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Showing 6351 - 6400Lung 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 ...
Prolyl Hydroxylase Inhibition Protects Against Gastrointestinal Radiation Toxicity
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...
BRCA2 Inhibits Genome Instability by Preventing R-Loop Accumulation
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...
Spleen Tyrosine Kinase Inhibition Has Promise in High-Risk Precursor B-Cell ALL
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...
Ibrutinib in Previously Treated CLL and CLL With 17p Deletion
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 28, 2014, the approved use of ibrutinib (Imbruvica) in...
Idelalisib for Relapsed CLL in Combination With Rituximab and for Relapsed Follicular Lymphoma or Small Lymphocytic 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 23, 2014, idelalisib (Zydelig) was approved for use in...
Minority of Older Patients With Low-Risk Prostate Cancer Managed by Observation, Rates Vary Widely Among Urologists and Radiation Oncologists
Most older men with low-risk prostate cancer receive upfront treatment, despite the absence of a clear survival benefit and potential for morbidity. In a retrospective cohort study reported in JAMA Internal Medicine, Karen E. Hoffman, MD, MHSc, MPH, of The University of Texas MD Anderson Cancer...
Early Change in Chemotherapy Based on Elevated Circulating Tumor Cells Does Not Improve Outcome in Metastatic Breast Cancer
Elevated circulating tumor cells are associated with poor prognosis in metastatic breast cancer. In a phase III trial (Southwest Oncology Group [SWOG] S0500) reported in Journal of Clinical Oncology, Jeffrey B. Smerage, MD, PhD, Clinical Associate Professor in Medical Oncology at the University of...
Adjuvant Endocrine Therapy for Hormone Receptor–Positive Breast Cancer: ASCO Clinical Practice Guideline Focused Update
ASCO has released a focused update of its clinical practice guideline on adjuvant endocrine therapy in women with hormone receptor–positive breast cancer.1 The focused update, formulated by Harold J. Burstein, MD, PhD, of Dana-Farber Cancer Institute, Boston, and colleagues in the ASCO Update...
PREVAIL Trial: Enzalutamide Before Chemotherapy Prolongs Survival in Metastatic Prostate Cancer
The androgen-receptor inhibitor enzalutamide (Xtandi) has been shown to prolong survival in men with metastatic castration-resistant prostate cancer with progressive disease after chemotherapy. In the phase III PREVAIL trial reported in The New England Journal of Medicine, Tomasz M. Beer, MD, of...
No Overall Survival Improvement but Some Palliative Benefit With Gefitinib in Esophageal Cancer Progressing Postchemotherapy
In what may be the first randomized trial of systemic therapy in this setting, Susan J. Dutton, MSc, of University of Oxford, United Kingdom, and colleagues evaluated the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib vs placebo in patients with esophageal cancer...
15-PGDH Expression in Normal Mucosa May Be Biomarker for Aspirin Prevention of Colorectal Cancer
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...
Small Molecule Induces Catastrophic Vacuolization and Death of Glioblastoma Cells
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...
Dysregulated Cell-Cycle Progression and Akt Hyperactivation in Cancer
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 ...
Fusion Protein Improves Dendritic Cell Penetration, Raising Prospect of Efficient Cancer Vaccine
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...
BET Bromodomain Inhibition Highly Active in Castration-Resistant Prostate Cancer
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...
Phase III Trial of Figitumumab Plus Chemotherapy in Advanced NSCLC Stopped Early for Futility and Increased Harm
In the first phase III trial assessing the combination of an insulin-like growth factor 1 receptor (IGF-1R) inhibitor with chemotherapy as first-line treatment for advanced nonadenocarcinoma non–small cell lung cancer (NSCLC), the addition of the fully human immunoglobulin G2 monoclonal antibody...
Lung Screening–Detected Abnormalities Other Than Cancer Result in Smoking Cessation: National Lung Screening Trial Analysis
In a study reported in the Journal of the National Cancer Institute, Martin C. Tammemägi, PhD, of Brock University, Ontario, and colleagues assessed smoking cessation rates among participants undergoing chest x-ray or computed tomography (CT) screening for lung cancer in the National Lung Screening ...
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...
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...
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...
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...
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 ...
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,...
