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Showing 801 - 850shRNAs Can Identify T-Cell Inhibitory Mechanisms in Tumor Microenvironment
Although recent findings indicate that targeting of inhibitory receptors on T cells can produce durable responses in some cancer patients despite the presence of advanced disease, the mechanisms controlling T-cell function in immunosuppressive tumors have not been well characterized. In a study...
Mutation Predicts Benefit From Alkylating Chemotherapy in Oligodendroglial Tumors
Patients in the Radiation Therapy Oncology Group (RTOG) 9402 study with 1p/19q codeleted anaplastic oligodendroglial tumors had markedly prolonged overall survival after chemoradiotherapy (with procarbazine, lomustine, and vincristine) compared with radiation therapy alone. Some patients with...
Antioxidants Accelerate Lung Cancer Progression and Reduce Survival in Mice
Clinical trials of antioxidants in cancer have yielded inconsistent results. In a study reported in Science Translational Medicine, Sayin and colleagues evaluated the effects of the antioxidants N-acetylcysteine and vitamin E in mouse models of BRAF- and KRAS-induced lung cancer. N-acetylcysteine...
Synergy of IAP Antagonist and Demethylating Agents Against AML Stem/Progenitor Cells
In a study reported in the Journal of the National Cancer Institute, Carter and colleagues identified deregulated apoptotic components in acute myeloid leukemia (AML) stem/progenitor cells and investigated the effects of the novel inhibitor of apoptosis (IAP) protein antagonist and SMAC mimetic...
Informed Consent: Not Just About Blood Tests and Procedures Anymore
On February 24, the Institute of Medicine National Cancer Policy Forum convened a workshop, “Contemporary Issues in Human Subjects Protection in Cancer Research,” in Washington, DC. In his introduction to the workshop, Steven Piantadosi, MD, PhD, Director, Samuel Oschin Cancer Institute,...
Targeting Cancer Stem Cells in Breast Cancer: A Potential Clinical Strategy
Preclinical models have suggested that cancer stem cells play a role in tumor recurrence and metastasis following adjuvant therapy, and Max S. Wicha, MD, and his research team are deciphering the mechanisms by which this might happen. A true understanding of cancer stem cells will have important...
Conquering Colorectal Cancer With Sanjay Goel, MD, the 2010 Advanced Clinical Research Award in Colorectal Cancer Recipient
Colorectal cancer is the third most common cancer diagnosed in both men and women in the United States, and about 1 in 20 individuals will develop colorectal cancer in their lifetime. The good news is that improvements in screening, earlier detection, and treatments are all leading to improved...
Breaking Bad News Badly Can Add to Upset
When the prognosis is poor, breaking the bad news badly can exacerbate the distress experienced by cancer patients and their families. A lack of sensitivity to patient and family emotions and not being attuned to how individual patients would prefer to be informed about their prognoses can result...
New p53-Dependent Gene Cooperates With p53 in Tumor-Suppressor Functions
The TP53 tumor-suppressor gene influences genomic stability, apoptosis, autophagy, response to stress, and DNA damage, and identification of new p53-target genes could help elucidate mechanisms through which p53 controls cell integrity and response to damage. As reported in Journal of the National...
DNA Repair Pathway Recombination Proficiency Score Correlates With Tumor Sensitivity to Chemotherapy
As reported in Science Translational Medicine, Pitroda and colleagues developed a recombination proficiency score that measures the efficiency of DNA repair pathways in the context of cancer therapy aimed at generating DNA damage. The score is based on expression levels of four genes involved in...
Epigenetic Reprogramming of HOXC10 Results in Endocrine Resistance in Breast Cancer
Resistance to aromatase inhibitors is a major problem in treatment of estrogen receptor (ER)-positive breast cancer. In a study reported in Science Translational Medicine, Pathiraja and colleagues found pervasive DNA hyper- and hypomethylation and enrichment for promoter hypermethylation of...
IL-17A Promotes and GM-CSF Suppresses Circulating Tumor Cells and Metastasis in Colorectal Cancer
In a study of the roles of interleukin (IL)-17A and circulating tumor cells in colorectal cancer metastasis, Tseng and colleagues measured mesenteric circulating tumor cells according to colorectal cancer stage in patients and assessed the interaction of circulating tumor cells and IL-17A in a...
IL-15 Deletion Linked to Reduced Local Proliferation of B and T Cells and Poorer Outcome in Colorectal Cancer
The tumor microenvironment contains a complex network of cytokines that contribute to the nature of intratumoral immune reactions. In a study reported in Science Translational Medicine, Mlecnik and colleagues assessed chromosomal gains and losses and expression of 59 cytokines and receptors and...
Inactivation of E3 Ubiquitin Ligase Cbl-b Allows Natural Killer Cells to Control Metastases
New therapeutic approaches to blocking inhibitory pathways of the immune system have raised hopes that such treatments might thwart development of metastases. In a study in Nature, Paolino and colleagues have shown that genetic deletion of the E3 ubiquitin ligase Cbl-b (casitas B-lineage...
PPAR-δ/β Overexpression Increases Colon Tumorigenesis
Although it is known that nuclear receptor peroxisome proliferator-activated receptor-δ/β (PPAR-d) is upregulated in colorectal cancer, the role of PPAR-d in tumorigenesis remains uncertain. In a study reported in Journal of the National Cancer Institute, Zuo and colleagues developed a mouse model...
The Promise of Genomics
My year as President of ASCO was one of momentous change, not just for ASCO, but for health care and for cancer biology as well. The theme of my Presidency was Patients, Pathways, and Progress. “Pathways” referred to the molecular pathways that are becoming increasingly important in the targeted...
Guidelines for Chemotherapy-Induced Neuropathy: The Known Unknowns
It is a tribute to the advances in supportive care that peripheral neuropathy, along with fatigue, has become the most vexing management challenge in cancer patients receiving chemotherapy. The successes of modern antiemetic regimens and white blood cell growth factor support have radically altered ...
Janet L. Rowley, MD: April 5, 1925–December 17, 2013
Dr. Janet L. Rowley’s groundbreaking research in the translocation of genetic material bucked scientific convention and heralded a new understanding that cancer is indeed a genetic disease. Her research was largely responsible for the discoveries that led to the development of the targeted cancer...
Geoffrey P. Herzig, MD: December 6, 1941–December 20, 2013
Many of the advances that have bettered mankind are attributed to those who were driven by a primary passion. Geoffrey P. Herzig, MD, lived the better part of his life with a primary passion: conducting research to increase the cure rate of leukemia and lymphoma patients. His friend and colleague,...
Donald L. Morton, MD: September 12, 1934–January 10, 2014
Donald L. Morton, MD, transformed the management of melanoma and breast cancer by introducing the sentinel node biopsy, giving surgeons an accurate roadmap for treatment, and sparing generations of cancer patients from the morbidity associated with unnecessary surgery. Throughout his distinguished...
Peter Jacobs, MD, PhD: 1934–2013
Peter Jacobs, MD, PhD, regarded as the father of hematology in his native country of South Africa, began each day at 3 AM in the gym. During his workout, Dr. Jacobs would routinely call the nursing staff for updates on patients in his ward. Before sunup, Dr. Jacobs was on his way to the hospital....
Understanding the Relationship Between the Lab and the Clinic is Key to 2014 Karnofsky Memorial Award Honoree’s Success
The island nation of Curaçao is nestled in the southern Caribbean Sea off the Venezuelan coast. Curaçao was first settled by the Arawaks, an Amerindian people that inhabited the island for hundreds of years before the arrival of Europeans. Amid one wave of settlers from Portugal and Spain that...
Enthusiasm and Vision Guide the Head of FDA’s Oncology Office
In 2005, Richard Pazdur, MD, was named the FDA’s Director of the Office of Hematology and Oncology Products. By any measure, being arbiter of the nation’s oncology drug pipeline is a daunting prospect, but Dr. Pazdur sees it as an opportunity to encourage his talented staff to work for the greater ...
A Coast-to-Coast Road to an Illustrious Career in Radiation Oncology
Nationally regarded radiation oncologist and lymphoma expert Richard Hoppe, MD, was reared in Seaford, a small town hugging the South Shore of Long Island, New York. “I grew up in the early part of Long Island’s suburban sprawl, and my childhood was a fairly typical experience for that time,”...
ASCO Past President and Breast Cancer Researcher Works to Unite the Oncology Community in the Fight Against Cancer
World-renowned breast cancer researcher, Nancy E. Davidson, MD, was born in Denver, Colorado, the daughter of two geologists. “My mother was a geologist beginning in the 1940s, a time when women really didn’t pursue that kind of career. So, I was reared in a very scientifically oriented...
An Early Calling to Medicine That Never Wavered: ASCO President Peter P. Yu, MD
The road leading to a career in medicine is often a stepwise journey of multiple decision points and influences. However, sometimes the decision to become a doctor is hardwired from birth. Such was the case with 2014-2015 ASCO President Peter P. Yu, MD. Since his days in nursery school, Dr. Yu...
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...
Druggable Oncogene Fusions Found in KRAS Wild-Type Lung Invasive Mucinous Adenocarcinoma
As reported in Clinical Cancer Research, Nakaoku and colleagues identified oncogene fusions that function as driver mutations in KRAS wild-type invasive mucinous adenocarcinoma of the lung. Whole-transcriptome sequencing of 32 invasive mucinous adenocarcinomas, including 27 without KRAS mutations,...
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...
Copper Chelation for BRAF-Mutated Disease?
The V600E mutation in BRAF kinase is associated with oncogenesis in melanoma and other cancers. BRAF V600E phosphorylates and activates MEK1 and MEK2 kinases, which phosphorylate and activate ERK1 and ERK2 kinases, resulting in activation of the MAPK pathway. The addition of a BRAF V600E inhibitor...
Aflibercept More Active Than Bevacizumab in Patient-Derived Colorectal Cancer Xenografts
Some evidence suggests that dual targeting of vascular endothelial growth factor (VEGF) and placental growth factor (which binds to VEGFR-1) might provide more effective antiangiogenic therapy. In a study reported in Molecular Cancer Therapeutics, Chiron and colleagues compared the antitumor...
New Option for Preserving Fertility in Women Being Treated With Chemotherapy for Early-Stage Breast Cancer
One of the most reported studies emanating from the 2014 ASCO Annual Meeting involves the use of the luteinizing hormone–releasing hormone (LHRH) agonist goserelin (Zoladex) to reduce the risk of ovarian failure among women being treated with chemotherapy for early-stage breast cancer, and to...
Conquering Cancer With 2013 Career Development Award Recipient Rebecca A. Gardner, MD
Rebecca A. Gardner, MD is an Assistant Professor at the University of Washington and Attending Physician at Seattle Children’s Hospital. She received a 2013 Conquer Cancer Foundation of ASCO Career Development Award (CDA) for her project “Autologous T cells genetically modified to express a CD19...
Expert Point of View: Sherene Loi, MD PhD
Sherene Loi, MD PhD, Head of the Translational Breast Cancer Genomics Lab at the Peter McCallum Cancer Centre, Victoria, Australia, commented on the N9831 study presentation and referred to her group’s own work on tumor-infiltrating lymphocytes. These investigators have shown a positive association ...
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...
From Ireland to America and Back, Patrick G. Johnston, MD, PhD, Thrives on Bringing Research Findings to Clinical Practice
Patrick G. Johnston, MD, PhD, FMedSci, Professor of Oncology and President and Vice-Chancellor of Queen’s University Belfast, grew up in Derry, a city in Northern Ireland. Derry is distinct in being Ireland’s only remaining fully intact walled city, considered one of the finest examples of a walled ...
The Road to Progress in Lung Cancer Treatment
Despite promising new agents and therapeutic approaches, 5-year lung cancer survival rates have lagged far behind those of most other malignancies. To shed light on some of the important issues facing lung cancer experts, The ASCO Post recently spoke with internationally recognized lung cancer...
What Do Humans and Laboratory Rats Have in Common?
The requirements for sound evidence of a drug’s therapeutic benefit have translated laboratory experience to human testing. In the laboratory, experimental animals give their lives to lethal testing of drugs and scientific analysis. LD50, the terminology denoting an anticipated 50% death rate of...
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...
