DNA Gaps in Breast and Ovarian Cancer Cells Open the Door for New Treatment Options
A new paper in Molecular Cell highlights the work of the Ciccia laboratory, demonstrating a novel vulnerability in certain breast and ovarian cancer cells, and potentially opening the door to new treatment options.
Alberto Ciccia, PhD, serves as an associate professor in the Department of Genetics and Development. His laboratory uncovers the mechanisms by which the DNA damage response (DDR) protects the genome from insults induced by endogenous and exogenous stimuli. The DDR plays a critical role in human disease, and mutations in DDR genes cause more than 40 genetic disorders, including multiple cancers. In the recently published work, Angelo Taglialatela, PhD, associate research scientist and first author of the paper, discovered that human cancer cells deficient in the key DNA repair genes BRCA1 and BRCA2, mutations of which are common in familial breast and ovarian cancer, accumulate single-strand DNA gaps during normal DNA replication, a vulnerability that could be exploited if new treatment options are developed.
“Overall, we found a DNA lesion in BRCA1/2-deficient cells that is formed during normal growth. This lesion could be relevant for breast and ovarian cancer etiology,” says Dr. Ciccia. “We discovered that this lesion renders BRCA1/2-deficient cancer cells addicted to the DNA polymerases REV1 and Polzeta for its repair, providing a new therapeutic opportunity for these tumor cells.”
Exploiting vulnerabilities in cancer cells is one of the key approaches scientists can use to beat cancer at its own game. This new research shows that there is the potential to develop new effective treatments to target a previously unknown vulnerability. New treatments may also help overcome the development of resistance to other treatments in BRCA1/2-mutant cancers, putting patients and their doctors a step ahead.