Sneha Saxena, PhD
Massachusetts General Hospital
2022 James A. Harting Scientific Scholar Award
Targeting ovarian cancer by exploiting a novel type of replication stress induced by unprocessed uracil in DNA
Despite decades of work to develop new treatments, the five-year survival of patients with advanced ovarian cancer is between 10-30 percent. Hence, there is a pressing need to identify more biomarkers for early detection and find new therapeutic targets. Dr. Saxena will tackle this by exploring an understudied source of stress in cancer cells. The nucleotide bases that are the building blocks of DNA can be sometimes modified by environmental agents, metabolic alterations, and certain enzymes. Most of these modified DNA bases are believed to be well-tolerated by human cells. However, cancer cells likely have unusually high numbers of base modifications, which could saturate the DNA repair pathways.
Dr. Saxena will study whether this accumulation of DNA base modifications in cancer cells disturbs cellular processes, like replication of the DNA. This knowledge could be exploited to develop novel anti-cancer drugs to enhance the clinical efficacy of existing drugs and to overcome drug resistance. Furthermore, this will help identify novel biomarkers to allow early detection of ovarian cancer and improve patient survival.