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Showing 6251 - 6300ASCO 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...
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...
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...
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...
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 ...
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...
Ramucirumab in Combination With Paclitaxel in Advanced Gastric or Gastroesophageal Junction Adenocarcinoma
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 November 5, 2014, ramucirumab (Cyramza) was approved for use...
ASCO Endorses Guideline for Molecular Testing for Selecting Lung Cancer Patients for EGFR and ALK Inhibitor Treatment
ASCO has endorsed the recently developed joint College of American Pathologists (CAP), International Association for the Study of Lung Cancer (IASLC), and Association for Molecular Pathology (AMP) guideline on molecular testing for selection of patients with lung cancer for EGFR and ALK inhibitor...
Kinase-Activating Alterations Identified in Most Cases of Philadelphia Chromosome–Like Acute Lymphoblastic Leukemia May Be Targetable With Available Tyrosine Kinase Inhibitors
In a study reported in The New England Journal of Medicine, Kathryn G. Roberts, PhD, of St. Jude Children’s Research Hospital, and colleagues performed detailed genomic analysis of patients with Philadelphia chromosome–like acute lymphoblastic leukemia (ALL) and identified kinase-activating...
Adding VEGFR2 Inhibitor Ramucirumab to Paclitaxel Increases Overall Survival as Second-Line Treatment for Advanced Gastric Cancer
In the phase III RAINBOW trial reported in The Lancet Oncology, Hansjochen Wilke, MD, Director of Medical Oncology/Hematology at Kliniken Essen-Mitte, Essen, Germany, and colleagues found that adding the vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor ramucirumab (Cyramza) to...
Two Phase III Trials Show Benefit With BRAF/MEK Inhibitor Combination vs BRAF Inhibitor Alone in Advanced Melanoma
Two phase III trials have shown that the strategy of adding MEK inhibitor therapy to BRAF inhibitor therapy significantly improves progression-free survival in previously untreated patients with advanced BRAF-mutant melanoma.1,2 Overall survival benefit is also suggested by interim analysis in both ...
Long-Term Overall Survival Benefit Seen With Trastuzumab Added to Adjuvant Chemotherapy in Early-Stage HER2-Positive Breast Cancer
Earlier planned joint analyses of outcomes in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31 trial and the North Central Cancer Treatment Group (NCCTG) N9831 trial showed that adding trastuzumab (Herceptin) to adjuvant chemotherapy improved disease-free survival and overall...
Impact of High-Dose Melphalan/Autologous Stem Cell Transplant and Lenalidomide Maintenance in Myeloma Patients ≤ Age 65
In a phase III trial reported in The New England Journal of Medicine, Antonio Palumbo, MD, Chief of the Myeloma Unit at the University of Turin, Italy, and colleagues found that high-dose melphalan plus autologous stem cell transplantation improved progression-free survival and overall survival...
Vigorous Exercise Lowers Risk of Cardiovascular Events in Adult Survivors of Childhood Hodgkin Lymphoma
In a report from the Childhood Cancer Survivor Study published in the Journal of Clinical Oncology,1 Lee W. Jones, PhD, of Memorial Sloan Kettering Cancer Center, and colleagues found that vigorous exercise reduces the risk of major cardiovascular events in adult survivors of childhood Hodgkin...
Fixed-Combination Netupitant/Palonosetron for Prevention of Chemotherapy-Induced Nausea and Vomiting
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 October 10, 2014, oral fixed-combination netupitant and...
Bortezomib in Previously Untreated Mantle 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 October 9, 2014, bortezomib (Velcade) was granted approval for ...
Pazopanib Maintenance Improves Progression-Free Survival in Ovarian Cancer
In a phase III trial reported in the Journal of Clinical Oncology, Andreas du Bois, MD, PhD, Professor of Gynecologic Oncology at Kliniken Essen-Mitte in Essen, Germany, and colleagues found that maintenance therapy with the vascular endothelial growth factor receptor (VEGFR) and platelet-derived...
Study Finds Significant Increase in Bilateral Mastectomy for Unilateral Breast Cancer Despite Lack of Survival Benefit
In an observational cohort study reported in JAMA, Allison W. Kurian, MD, MSc, Assistant Professor of Medicine and of Health Research and Policy at Stanford University School of Medicine, and colleagues assessed use of and mortality after bilateral mastectomy, breast-conserving surgery plus...
Continuous Lenalidomide/Dexamethasone Improves Progression-Free Survival in Transplant-Ineligible Patients With Myeloma
In the phase III FIRST trial reported in The New England Journal of Medicine, Lotfi Benboubker, MD, Service d’Hématologie et Thérapie Cellulaire, Hôpital Bretonneau, Centre Hospitalier Régional Universitaire (CHRU), Tours, France, and colleagues found that continuous lenalidomide (Revlimid) plus...
Oral Rivaroxaban Has Efficacy Similar to Enoxaparin Plus Vitamin K Antagonist in Preventing Recurrent Venous Thromboembolism
In a subgroup analysis of the pooled results of the EINSTEIN-DVT and EINSTEIN-PE trials reported at the 2014 European Society for Medical Oncology (ESMO) 2014 Congress and published recently in The Lancet Haematology, Martin H. Prins, MD, of Maastricht University Medical Centre, Maastricht,...
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 ...
Adding Pan-Deacetylase Inhibitor Panobinostat to Bortezomib and Dexamethasone Improves Progression-Free Survival in Relapsed Myeloma
In the phase III PANORAMA 1 trial reported in The Lancet Oncology, Jesus F. San-Miguel, MD, of Clinica Universidad de Navarra-CIMA, Pamplona, Spain, and colleagues found that adding the pan-deacetylase inhibitor panobinostat to bortezomib (Velcade) and dexamethasone improved progression-free...
Systemic Therapy in Men With Metastatic Castration-Resistant Prostate Cancer: ASCO/CCO Clinical Practice Guideline
The ASCO Clinical Practice Guidelines Committee and the Cancer Care Ontario (CCO) program in evidence-based care have released a clinical practice guideline on systemic therapy in men with metastatic castration-resistant prostate cancer. The guideline was published in the Journal of Clinical...
NORCCAP Trial Shows Reduced Colorectal Cancer Incidence and Mortality With Flexible Sigmoidoscopy Screening at 11 Years
The Norwegian Colorectal Cancer Prevention (NORCCAP) trial comparing colorectal cancer screening with flexible sigmoidoscopy vs no screening showed no reduction in colorectal cancer incidence or mortality after 7 years of follow-up. As reported by Øyvind Holme, MD, of Sorlandet Hospital...
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...
Predicting Immunogenic Tumor Neoantigens With Combined Mass Spectrometry and Exome Sequencing
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...
PD-L1 Expression by Tumor-Infiltrating Cells Associated With Activity of Anti–PD-L1 Antibody in Multiple Cancer Types
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 ...
WEE1 Inhibition Sensitizes Pancreatic Cancer to PARP Inhibitor Radiosensitization
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...
Checkpoint Blockade Immunotherapy Targets Tumor-Specific Mutant Antigens
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,...
Intraperitoneal Oxidative Stress Induces Tumoricidal Immune Response in Papillomavirus-Linked Head/Neck Cancer
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...
Dual HER2 Targeting Inhibits HER2-Amplified Uterine Serous Carcinoma
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...
Lipophilic Bisphosphonate Plus Rapamycin Active in KRAS-Mutant Lung Cancer
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...
Functional Kinomics Identifies WEE1 Kinase as Target in Head and Neck Cancer
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...
