Masood Shammas, Ph.D., director of Surgical Oncology and the Developmental Therapeutics Laboratory of the Karmanos Cancer Institute and Department of Surgery at the Wayne State University School of Medicine, received a National Cancer Institute R01 award for his project, “Telomerase and Homologous Recombination as Targets in Barrett’s Adenocarcinoma.” Dr. Shammas will receive $1.8 million in funding over the next five years.

Working on the project with Dr. Shammas are Ramesh Batchu, Ph.D., associate director of the Surgical Oncology and Developmental Therapeutics laboratory at the Karmanos Cancer Institute and assistant professor of surgery at the School of Medicine; and Madhu Prasad, M.D., co-chief of Surgical Oncology at Karmanos and associate professor of surgery at the School of Medicine.

The funding from this award will allow Dr. Shammas’ lab to study telomeres, telomerase, and homologous recombination in the development and progression of Barrett’s esophageal adenocarcinoma (BEAC), a cancer associated with heartburn. Telomeres are the ends of chromosomes, the structures carrying genetic material or DNA. Normal human cells lose a portion of telomeric DNA each time a cell divides. As soon as the average length of telomeres in a cell dips below a critical limit, the cell dies. Cancer cells acquire the ability to maintain their telomeres at a specific length and therefore can continue to grow. The maintenance of telomeres in cancer cells is either achieved by activation of a protein called telomerase or by a process of genetic rearrangement, called homologous recombination. The lab will also test the inhibitors of telomerase and recombination, separately and together, for prevention and treatment of BEAC in mice.

"In this proposal we plan to investigate the roles of both telomerase and homologous recombination (HR), in development of Barrett’s esophageal adenocarcinoma, and to evaluate inhibitors of these pathways in prevention and treatment of this disease,” Dr. Shammas explained. “We will also identify combinations of inhibitors which completely block telomere expansion, by inhibiting both telomerase- and HR-dependent maintenance of telomeres, in human BEAC cells.

“Such treatments may prove to be more effective in inducing telomere shortening and apoptosis in cancer cells by acting at multiple levels, with little or no detrimental effect on normal cells,” Dr. Shammas said. “Moreover, inhibitors of HR could also help in cancer chemo­therapy, by impeding phenotypic heterogeneity arising in tumors and tumor acquisition of new resistant phenotype which is associated with chromosomal instability."