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Showing 851 - 900Chemotherapy-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...
NCI Awards $2 Million Grant to University of Pittsburgh School of Dental Medicine to Study How Cancer Spreads to Bone
With a $2 million, 5-year grant from the National Cancer Institute (NCI), researchers at the University of Pittsburgh School of Dental Medicine will examine the molecular mechanisms that allow certain cancers, particularly multiple myeloma, to spread to the bone. The project could lead to new...
Clinical Trials Actively Recruiting Patients With Lung Cancer
The information contained in this Clinical Trials Resource Guide includes actively recruiting clinical studies of people with lung neoplasms, including stage I and II small cell and non–small cell lung cancers. The studies include phase Ib, II, III, observational, and interventional trials...
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...
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...
