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Research Round-ups

Understanding Kidney Cancer Progression

Understanding Kidney Cancer Progression—Clear cell renal cell carcinoma (CCRCC) is the most common type of kidney cancer. In a study published online on January 31 in the Journal of Clinical Investigation, Niraj Shenoy, MD., M.S., Amit K. Verma, M.B.B.S., and colleagues describe a new prognostic biomarker for this type of cancer called 5-hydroxymethylcytosine (5hmC). As kidney cancer advances, tumor levels of 5hmc progressively decrease. The researchers found that loss of 5hmC occurs because an aberrant metabolic intermediate inhibits enzymes called TET (Ten-eleven Translocation). Furthermore, the presence of ascorbic acid (Vitamin C) prevents the aberrant intermediate from affecting TET and restores 5hmC levels. High-dose intravenous ascorbic acid inhibited kidney cancer growth in a mouse model and increased 5hmc within the tumors. These findings have led to an ongoing multicenter randomized phase 2 clinical trial of vitamin C as an adjunct to standard of care treatment for metastatic and unresectable CCRCC. Dr. Verma is professor of medicine and of developmental and molecular biology at Einstein and attending physician in oncology at Montefiore Einstein Center for Cancer Care. Dr. Shenoy is an assistant professor of medicine at Einstein and attending physician in oncology at Montefiore Einstein Center for Cancer Care.

New Triple-Negative Breast Cancer Target

New Triple-Negative Breast Cancer Target—Up to 20 percent of breast cancers aretriple negative breast cancer (TNBC), an aggressive form of the disease with few treatment options. In looking for genes that promote TNBC metastasis and might be knocked out as a treatment strategy, Harry Ostrer, M.D., and colleagues from Einstein and Montefiore identified Otoconin 90 (OC90)—a gene normally expressed in the ear’s cochlea to form the little calcium stones that help to control equilibrium. But the gene has been repurposed and over-expressed in TNBC as well as prostate and lung cancers to serve a novel and pernicious function. In a cohort of TNBC patients, the researchers found that the altered expression of three genes associated with OC90 overexpression —HMGA2, POLE2 and TRIB3—predicts a greater likelihood that the patients will die from the disease. The findings were published online on February 14 in PLOS ONE. Dr. Ostrer is professor of pathology and of pediatrics at Einstein.