breakthrough board scholar

could we overcome treatment resistance by better understanding the relationship between ovarian cancer cells and fat cells?

Ovarian cancer is the deadliest of all gynecologic cancers, with no effective screening, vague symptoms at presentation, high recurrence rate, and very few targeted therapies available after diagnosis. The treatment outcomes for ovarian cancer (OvCa) are very poor due to therapeutic resistance and relapsed OvCa is often observed in tissues with high fat content. It is not clear how current OvCa treatments affect fat tissues, or how fat cells cause resistance to OvCa therapies. Identifying these mechanisms is critical to overcoming therapeutic resistance in OvCa.

We know that a set of metabolic enzymes control the growth of both OvCa cells and fat cells and
that the inhibitors of these enzymes, called PARP inhibitors (PARPi), are successful, at least at first, at managing ovarian cancers. Responses to this treatment vary widely and the effects of changes in fat tissues when there is low treatment response have not yet been investigated. Additionally, the function of PARP enzymes is intricately related to the level of NAD metabolites, which work together to regulate both adipocyte (fat storage) cells and ovarian cancer cells. Dr. Challa hopes to better understand the molecular mechanisms underlying the regulation of NAD+ metabolism and PARP inhibitor response by adipocytes in ovarian cancer. She will use a variety of metabolic, biochemical, and cell biology techniques, as well as mouse models, to uncover the effect of PARP inhibitors on adipocytes. Her goals are to understand how adipocytes regulate therapeutic response in OvCa cells, and to test the efficacy of inhibiting this adipocyte–ovarian cancer crosstalk to achieve better treatment responses. Understanding how PARP inhibitors affect adipocytes will allow the design of new strategies to improve the efficacy of our current ovarian cancer treatments and potentially show a way to limit treatment resistance. With her Young Investigator Award, Dr. Challa hopes to fully explain the communication between fat cells and ovarian cancer cells and how their communication creates resistance to treatments.