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Showing 901 - 950RNA-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...
The Power of Laughter
The following essay by Julie Vose, MD, MBA, FASCO, is adapted from The Big Casino: America’s Best Cancer Doctors Share Their Most Powerful Stories (May 2014), coedited by Stan Winokur, MD, and Vincent Coppola. The book is available on Amazon.com and thebigcasino.org. When I met Cindy, she was...
Overutilization a Key Target in Efforts to Control Health-Care Costs
Overutilization of health-care interventions has become a prime target of efforts to rein in health-care costs. Overtreatment of cancer patients is associated with a number of common harms to the patient—not just financial harm to the health-care system. At the recent ASCO Quality Care Symposium in ...
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 ...
Memorial Sloan Kettering Team Discovery Advances Understanding of Immunotherapy’s Successes—and Its Failures
A collaborative team of leaders in the field of cancer immunology from Memorial Sloan Kettering Cancer Center has made a key discovery that advances the understanding of why some patients respond to the CTLA-4 blocking antibody ipilimumab (Yervoy), an immunotherapy drug, while others do not. A...
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...
Vincent T. DeVita, Jr, Helped Usher in the Era of Chemotherapy, Turning Lethal Cancers Into Curable Ones
Although Vincent T. DeVita, Jr, MD, harbored fantasies as a young child of becoming an ice deliveryman when he grew up, his love of chemistry and biology, as well as admonitions from his mother, Isabel, “to become a doctor,” propelled him toward a career in medicine. Now, more than 6 decades later, ...
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...
Breast Cancer Research Foundation Commits Record $58.6 Million in Research Grants
The Breast Cancer Research Foundation (BCRF) announced its dedication of $58.6 million to breast cancer research at its annual Symposium & Awards Luncheon. Totaling $47 million, the 2014–2015 annual grants, awarded to more than 220 physicians and scientists on six continents, continue to fuel...
‘Mother of Bone Marrow Transplantation’ Dorothy ‘Dottie’ Thomas Dies at 92
Dorothy “Dottie” Thomas, wife and research partner to 1990 Nobel laureate E. Donnall Thomas, MD, died Friday, January 9, at her home near Seattle. She was 92. Dr. Donnall Thomas, Pioneer of the Bone Marrow Transplant and former Director of the Clinical Research Division at Fred Hutchinson Cancer...
Blinatumomab Achieves Complete Molecular Responses in Majority of B-Cell Leukemia Patients
Results from the international phase II BLAST study show that one cycle of blinatumomab (Blincyto) immunotherapy achieved complete minimal residual disease response in 78% of patients with acute lymphoblastic leukemia.1 Complete minimal residual disease response was achieved in 80% of patients...
Molecular Pathologists vs the FDA: Proposed Regulation of Laboratory-Developed Tests Sparks Debate
The packed ballroom looked like a plenary session at any big medical research meeting. But on the dais were representatives of the Food and Drug Administration (FDA), the subject was the Agency’s proposed regulation of laboratory-developed tests, and the attendees who lined up to ask questions for...
Top 10 Lessons Learned So Far About Treating Lung Cancer With Immunotherapy
Immunotherapy agents “really work” in treating lung cancer, but they have unique toxicities, are challenging to combine with other therapies, and questions remain about dose and duration, Roy S. Herbst, MD, PhD, stated at the 2014 Chicago Multidisciplinary Symposium in Thoracic Oncology. “There are ...
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...
ASCO Endorsement of ESMO Guidelines on Hereditary Colorectal Cancer Syndromes
In a recent issue of the Journal of Clinical Oncology,1 and as reviewed in this issue of The ASCO Post, an ASCO expert endorsement panel reviewed and endorsed, with minor qualifications, the European Society for Medical Oncology (ESMO) clinical practice guidelines for management of familial/genetic ...
The Current State of Hematologic Malignancies
Due in part to the refinement of bone marrow transplantation and its many innovations, some leukemias that once were death sentences now have cure rates of up to 90%. As research in transplantation and other promising areas accelerates, we are on the verge of breaking new clinical boundaries in...
Jennifer Adair, PhD, Recognized as ‘Outstanding New Investigator’
Jennifer Adair, PhD, of the Fred Hutchinson Cancer Research Center, has been named a 2015 Outstanding New Investigator by the American Society of Gene & Cell Therapy (ASGCT). The award recognizes Dr. Adair’s independent research efforts to understand and improve blood stem cell–based gene...
FDA Grants Cobimetinib Priority Review for Use in Combination With Vemurafenib in Advanced Melanoma
The U.S. Food and Drug Administration (FDA) has accepted and granted Priority Review for Genentech’s New Drug Application (NDA) for cobimetinib in combination with vemurafenib (Zelboraf) for the treatment of people with BRAF V600 mutation–positive advanced melanoma. The FDA will make a decision on...
Medicine Turned Upside Down
BookmarkTitle: The Patient Will See You Now: The Future of Medicine Is in Your HandsAuthor: Eric Topol, MDPublisher: Basic BooksPublication date: January 2015Price: $28.99; hardcover, 384 pagesMost books about health care center on fixing broken parts of the massive $3 trillion system, as seen with ...
I Refuse to Capitulate to Cancer
Editor’s note: We regret to announce that Paul Kalanithi, MD, passed away on March 9, 2015. Dr. Kalanithi was Chief Resident in Neurological Surgery at Stanford University when he shared his story, reprinted here, with The ASCO Post just over 1 year ago, in March 2014. We extend our deepest...
Shining a Spotlight on Epithelioid Hemangioendothelioma
In the winter of 2013, my son, Dmitriy, now 26, had a cough that wouldn’t go away. After several rounds of antibiotics failed to halt the persistent problem, a pulmonologist we consulted ordered a chest x-ray, which showed a large tumor lodged between Dmitriy’s lungs. Although the doctor said the...
A Surgeon Cuts to the Chase
BookmarkTitle: The Cost of Cutting: A Surgeon Reveals the Truth Behind a Multibillion-Dollar IndustryAuthor: Paul A. Ruggieri, MDPublisher: Berkley BooksPublication date: September 2014Price: $16.00; paperback, 320 pages The woman seated on the exam table was lean and fit and seemed perfectly at...
Clinical Trial Participation: ‘Is It All Worth It?’
Clinical trials have become increasingly complex over the past several years, and unfortunately, this has resulted in the typical scenario described below. We are fortunate that there are so many promising agents available for patients, and we want to encourage their participation in clinical...
In Search of ‘Just’ Prices: Questioning the High Cost of New Cancer Drugs
As the oncology community begins the slow and often difficult-to-define transition from volume to value in the delivery of cancer care, the relationship between the price and value of certain high-priced cancer drugs is getting more scrutiny. We generally correlate the efficacy of a new drug and...
Researchers Discuss Pilot Study on Hallucinogenic Therapies for Cancer Anxiety
Although varying levels of existential distress are near-ubiquitous among patients with cancer, evidence-based interventions in this clinical area remain somewhat elusive. Seeking to explore novel approaches in the palliative care environment, New York University (NYU) School of Medicine principal...
p53 Takes Center Stage
BOOKMARKTitle: p53: The Gene That Cracked the Cancer CodeAuthor: Sue ArmstrongPublisher: Bloomsbury PublishingPublication date: November 20, 2014Price: $19.98; hardcover, 288 pages Completed in April 2003, the Human Genome Project was one of the greatest feats of scientific exploration, an inward ...
EGFR Amplification/Overexpression Associated With Improved Response of Glioblastoma to Metronomic Temozolomide
In a study reported in Journal of the National Cancer Institute, Cominelli and colleagues found that EGFR amplification/overexpression was associated with improved response of glioblastoma to adjuvant metronomic (every day of a 28 day cycle at a dosing of 50-75 mg/m2) but not standard (5...
IGF2 May Be Target in Colorectal Cancer With Stable Disease As Response to Anti-EGFR Therapy
In a study exploring the mechanisms of stabilized disease vs tumor regression with targeted anti–epidermal growth factor receptor (EGFR) therapy in colorectal cancer reported in Science Translational Medicine, Zanella and colleagues found that stable disease as response was characterized by...
Bispecific Antibody Recruitment to Increase Antitumor Activity of Adoptive T-Cell Transfer
In a study reported in the Journal of the National Cancer Institute, Kobold and colleagues assessed whether combining tumor-specific T cells modified with a marker antigen and a bispecific antibody that selectively recognizes transduced T cells and tumor cells could improve T-cell recruitment to...
Many Miles to Go: Targeted Treatment Based on Whole-Genome Sequencing
The ability to do genomic analysis of patients’ tumors holds great promise for revolutionizing cancer treatment, and genomics has already made some great strides. However, the Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) trial is a cautionary tale about the hurdles involved in...
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): 2015 Updates
For 2 decades, the NCCN Guidelines® have been recognized as the standard of cancer care in the United States, combining evidence, experience, and choice, so that multidisciplinary cancer treatment teams—including patients—are empowered to make informed decisions about cancer care,” said Robert W....
A Tribute to James F. Holland, MD, in Celebration of His 90th Birthday
Far and away the best prize that life has to offer is the chance to work hard at work worth doing. —Theodore Roosevelt Longevity, in and of itself, is not an accomplishment. Luck and good genes are just human lottery tickets. Most people fortunate enough to live long lives have a productive sweet ...
