Epithelial Ovarian Cancer (EOC) is the fifth most common cause of cancer-related death in American women with the third highest mortality:incidence ratio. One reason for the high mortality rate is the development of resistance to anti-cancer drugs. One understudied mechanism of drug resistant in cancer, is the ability of cells to temporarily enter an ‘inactive state’ (known as quiescence) and stop making new cells. These inactive cells are resistant to chemotherapy drugs that are designed to target rapidly growing cells. The ability of some hair follicle cells to enter this inactive state and resist the effects of chemotherapy is the reason why cancer patients regrow their hair after chemotherapy is stopped.
Unfortunately, very little is known about these inactive non-dividing cells in ovarian cancer in part due to the challenges of studying rare slow growing cells in a sea of rapidly growing cancer cells. The goal of this project is to understand the factors which regulate the transition of a subset of ovarian cancer cells to an inactive state to allow them to resist chemotherapy. We will use two specific approaches. First, we will determine if the factors that drive quiescence/chemotherapy resistance in the hair cells is similarly active in ovarian cancer cells. Second, we will use a novel bioengineered microfluidic chip to identify the rare inactive cancer cells (needle) in the haystack of otherwise rapidly growing cancer cells. These studies have the potential to inform new therapeutic targets to combat ovarian cancer chemotherapy resistance, reduce disease relapse, and thereby improve patient survival.