NFCR Translational Research: Stomach Cancer
New Treatment for Patients with Gastric Cancer in Phase I Clinical Trial
Ronald A. DePinho, M.D. Univ. of Texas MD Anderson Cancer Center, Houston, Texas
STAT3 is a major signaling protein in cells. It is hyperactivated in over 50% of cancers including gastric adenocarcinoma the main type of stomach cancer. This results in abnormal cell growth, escape from our immune system, metastasis (spreading), and other cancer-associated processes. The development of drugs to target STAT3 effectively has been a challenge for the research community, earning it the label of ‘undruggable’.
Ronald DePinho, M.D. and his colleagues used computer-based drug screening of hundreds of thousands of compounds to identify several candidates that inhibit STAT3 protein when tested in complex tumor models of breast and other various cancers.
NFCR support facilitated the final studies of the most promising inhibitor of STAT3. The new inhibitor drug is treating patients in an ongoing Phase I clinical trial to establish its safety and appropriate dose. Patients with gastric adenocarcinoma and other advanced cancers may be eligible to enroll in the trial of this new treatment.
BASIC RESEARCH PROJECTS
Dr. Wei Zhang has devoted his entire career to the pursuit of precision oncology – specifically to the key molecular and genomic events that drive the development and progression of cancer. The incidence of gastric cancer is high in Asia and other countries and it is increasing in the United States. In collaboration with the Tissue Bank Consortium in Asia and other scientists, Dr. Zhang’s team analyzed advanced genome-sequencing data from hundreds of gastric cancer samples and discovered defects in three cellular signaling pathways (BRCA2, Wnt and PI3-K-ERBB4). Several newly developed drugs that target these pathways have been tested in breast and ovarian cancers and may lead to improved treatments for stomach cancer patients.
Dr. Paul Schimmel and Dr. Xiang-Lei Yang, experts in the protein synthesizing enzymes Aminoacyl-tRNA synthetases (aaRS), also study the enzyme’s other unexpected roles. One aaRS, SerRS, thwarts cancer’s growth and may activate the immune system to inhibit tumor progression. Expression of SerRS positively correlates with greater survival in patients with esophageal, breast, rectal, brain, kidney, lung, and thyroid. SerRS may also be a suppressor of metastasis as enzyme levels are significantly decreased in breast tissue during metastasis. This critical research may lead to a novel way to cancer, offering patients hope for a new therapy. SerRS level could potentially be used as a negative biomarker for metastasis, guiding selection of patients in clinical trial.
