Development of Novel Treatments for Ovarian Cancer

Grants and Contracts Details

Description

Ovarian cancer is a deadly disease. More than 20,000 women will be diagnosed with and approximately 14,000 will die of ovarian cancer in 2022. In the front-line setting, women are treated with a platinum compound (cisplatin and its analogues) and paclitaxel, and although up to 80% will respond initially, the majority recur and present with platinum-resistant disease. There is currently no effective treatment for platinum-resistant ovarian cancer. To overcome resistance and address this unmet medical, we have developed novel gold compounds as a treatment strategy for women with platinum-resistant ovarian cancer. These gold compounds are tuned for mitochondrial localization, demonstrated to disrupt mitochondrial structure in cancer cells, decrease mitochondrial biogenesis, are cancer selective, and have significant anticancer activity across multiple cancer cell lines. Gold compounds also decrease mitochondrial structure proteins. We hypothesize that these compounds directly and selectively interact with mitochondrial membranes resulting in reduced structural proteins (DRP1) and will adversely impact cancer cell energy pathways. The overall goal of our research is to evaluate the ability of mitochondrial targeting gold- based compounds to overcome platinum resistant ovarian cancer. In this proposal we will evaluate the activity of gold compounds on cell proliferation and cytotoxicity in ovarian cancer organoids (Aim 1). We will then evaluate the most active gold compounds in platinum sensitive and resistant ovarian xenografts (Aim 2). In both aims we will assess mitochondrial bioenergetics and function through mitochondrial respiration and stable isotope resolved (SIRM) metabolomics studies. Taken together, this application is highly innovative, evaluating a novel class of compounds in ovarian cancer, clinical relevant, using patient derived organoids and mechanistically important, providing key insights into the action of gold compounds on cellular metabolism.
StatusActive
Effective start/end date6/1/226/30/24

Funding

  • Markey Cancer Center Foundation: $50,000.00

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