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Showing 6451 - 6500mTOR 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...
Phase II Study Shows Improved Survival With Addition of Sargramostim to Ipilimumab in Metastatic Melanoma
Use of the granulocyte-macrophage colony-stimulating factor (GM-CSF) sargramostim (Leukine) together with the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) inhibitor ipilimumab (Yervoy) prolonged overall survival but not progression-free survival in patients with metastatic melanoma,...
Crizotinib Is Highly Active in ROS1-Rearranged NSCLC
Crizotinib (Xalkori) produced a high response rate and durable responses in patients with ROS1-rearranged non–small cell lung cancer (NSCLC), according to a study reported in The New England Journal of Medicine.1 Lead authors Alice T. Shaw, MD, PhD, of Massachusetts General Hospital Cancer Center,...
ASCO Clinical Expert Statement on Cancer Survivorship Care Planning
Efforts at implementing survivorship care plans have met with limited success in oncology practice, in part due to the time required to complete them, the lack of role clarity, and the lack of reimbursement for time to complete the documents. In response, ASCO convened a Survivorship Care Planning...
SIO Clinical Practice Guidelines on the Use of Integrative Therapies as Supportive Care in Patients Treated for Breast Cancer
The Society for Integrative Oncology (SIO) Guidelines Working Group has recently released clinical practice guidelines on the use of integrative therapies as supportive care in patients receiving treatment for breast cancer. The guidelines, reported by Heather Greenlee, ND, PhD, MPH, of Mailman...
Olaparib for BRCA-Mutated Previously Treated Advanced Ovarian 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 December 19, 2014, olaparib (Lynparza) was granted accelerated...
Gardasil 9 Adds Protection Against Cancer Caused by Additional Human Papillomavirus Types
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 December 10, 2014, Gardasil 9 (human papillomavirus 9-valent...
No Benefit of Adding Lapatinib to Fulvestrant in Hormone Receptor–Positive Advanced Breast Cancer
In a phase III trial (Cancer and Leukemia Group B [CALGB] 40302/Alliance) reported in the Journal of Clinical Oncology, Harold J. Burstein, MD, PhD, of Dana-Farber Cancer Institute, Boston, and colleagues found that the addition of the dual EGFR-HER2 inhibitor lapatinib (Tykerb) to endocrine...
Lanreotide in Gastroenteropancreatic Neuroendocrine Tumors
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 December 16, 2014, lanreotide (Somatuline depot injection) was ...
Nivolumab Improves Outcomes vs Dacarbazine in Previously Untreated Advanced Melanoma Without a BRAF Mutation
In a phase III trial reported in The New England Journal of Medicine, Robert and colleagues found that the programmed cell death protein-1 (PD-1) immune-checkpoint–inhibitor antibody nivolumab (Opdivo) significantly increased overall survival, progression-free survival, and objective response rate...
Anti–PD-1 Antibody Nivolumab in Previously Treated 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 December 22, 2014, the anti–PD-1 (programmed cell death...
Adding CD47 to Artificial Antigen-Presenting Cells May Stimulate T-Cell Responses and Improve Functionality
Artificial antigen-presenting cells have been shown to stimulate antigen-specific T-cell responses, but their effect in vivo may be compromised by rapid macrophage clearance. In a study reported in Clinical Cancer Research, Bruns and colleagues added CD47 to classic two-signal artificial...
Therapeutic DNA Vaccination Against Colorectal Cancer via MYB Targeting
The oncoprotein and transcription factor MYB is overexpressed in colorectal cancer and critical to proliferation and tumor cell survival. In a study reported in Clinical & Translational Immunology, Cross and colleagues developed a DNA vaccine to generate an MYB-specific immune response on the...
Zoledronic Acid Inhibits Angiogenesis in Ovarian Cancer Patients
The bisphosphonate zoledronic acid has been reported to produce antitumor effects, although the mechanisms of such effects remain unclear. In a study reported in Clinical Cancer Research, Gonzalez-Villasana and colleagues found evidence that zoledronic acid inhibited ovarian cancer angiogenesis by...
LAMC2 Increases the Metastatic Potential of Lung Adenocarcinoma
Mechanisms of lung cancer metastasis remain largely undefined. In a study reported in Cell Death & Differentiation that used genome-wide transcriptional analysis in a metastasis model, Moon and colleagues found that the epithelial basement membrane protein laminin γ2 (LAMC2) was significantly...
PEDF Improves Lung Cancer Response to Radiation via Vasculature Normalization
In a study reported in Cancer Gene Therapy, Xu and colleagues found that the addition of pigment epithelium-derived factor (PEDF) to radiation improved tumor response in a mouse model of lung cancer. Lewis lung cancer allografts in nude mice were treated with radiation, PEDF, and PEDF plus...
'Bipolar' Androgen Therapy in Castration-Resistant Prostate Cancer
Resistance to castrating therapy and androgen deprivation therapy in prostate cancer is due in part to adaptive upregulation of androgen receptor levels by castration-resistant prostate cancer cells in the setting of prolonged exposure to a low-testosterone environment. In a study reported in...
Ramucirumab in Metastatic Non–Small Cell Lung 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. In December 12, 2014, ramucirumab (Cyramza) was approved for use in ...
Novel Genomic Signature Predicts Postcystectomy Recurrence in High-Risk Bladder Cancer
As reported in the Journal of the National Cancer Institute, Anirban P. Mitra, MD, PhD, of the University of Southern California, and colleagues identified a novel genome-based signature that improves prediction of postcystectomy recurrence in patients with high-risk bladder cancer.1 Use of the...
Ruxolitinib for Polycythemia Vera
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 December 4, 2014, ruxolitinib (Jakafi) was approved for the...
No Benefit of Adding Iniparib to Gemcitabine/Carboplatin in Metastatic Triple‑Negative Breast Cancer
In a phase III trial reported in Journal of Clinical Oncology, Joyce O’Shaughnessy, MD, of Baylor Charles A. Sammons Cancer Center, Dallas, and colleagues found that the addition of iniparib to gemcitabine and carboplatin did not improve overall survival or progression-free survival in patients...
New Product May Help to Reduce Non-Compliance
A novel product created to help reduce medication non-adherence was recently recognized by the 2014 Pharma Choice Awards as the top innovative branded technology. The product, called “remind-a-cap” is a customizable and patented pill bottle cap with an ergonomic dial to set for next dosing. The cap ...
ASCO Endorses ESMO Guideline on Hereditary Colorectal Cancer Syndromes
Approximately 5% to 6% of cases of colorectal cancer are associated with germline mutations conferring an inherited predisposition for disease. As reported by Stoffel and colleagues in the Journal of Clinical Oncology,1 ASCO has endorsed, with qualifying statements, the European Society for Medical ...
Palbociclib as Initial Endocrine-Based Therapy in Postmenopausal Women With Metastatic Breast 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 February 3, 2015, palbociclib (Ibrance) was granted...
PD-1 Blockade With Nivolumab Produces High Response Rate in Relapsed/Refractory Hodgkin Lymphoma
Anti–PD-1 antibodies have been shown to be effective in solid tumors. There is evidence that the malignant Reed-Sternberg cells in Hodgkin lymphomas use the programmed cell death protein 1 (PD-1) pathway to evade immune detection, with alterations in chromosome 9p24.1 increasing levels of the PD-1...
Combination Treatment Every 2 Weeks May Benefit Some Women With High-Risk Early-Stage Breast Cancer
In a phase III trial (SWOG S0221) reported in the Journal of Clinical Oncology, George T. Budd, MD, of Taussig Cancer Center, Cleveland Clinic, and colleagues found no difference in disease-free survival among four different combinations of continuous or every-other-week...
Clonal Hematopoiesis With Somatic Mutations Increases Risk of Hematologic Cancer, Mortality, and Cardiovascular Disease
In two studies recently reported in The New England Journal of Medicine,1,2 whole-exome sequencing of DNA from peripheral blood cells of individuals unselected for hematologic phenotype showed that clonal hematopoiesis with somatic mutations is increasingly common with increasing age and is...
First-Line Crizotinib Improves Progression-Free Survival vs Chemotherapy in ALK-Positive NSCLC
In a phase III trial (PROFILE 1014) reported in The New England Journal of Medicine, Benjamin J. Solomon, MB, BS, PhD, of Peter MacCallum Cancer Centre, Melbourne, and colleagues found that the ALK inhibitor crizotinib (Xalkori) improved progression-free survival vs standard chemotherapy in...
Lenvatinib in Advanced Radioiodine-Refractory Differentiated Thyroid 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 February 13, 2015, lenvatinib (Lenvima) was approved for the...
Nivolumab Shows Activity in Previously Treated Metastatic Renal Cell Carcinoma
In a randomized phase II trial reported in the Journal of Clinical Oncology, Robert J. Motzer, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues found that the programmed cell death protein-1 (PD-1) immune checkpoint inhibitor antibody nivolumab (Opdivo) was associated with...
Panobinostat in Combination With Bortezomib‑Dexamethasone in Previously Treated 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 February 23, 2015, panobinostat (Farydak) was granted...
Lenalidomide in Combination With Dexamethasone in Newly Diagnosed 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 February 18, 2015, the indication for lenalidomide (Revlimid)...
