Cody Wolf

Developing New Drugs to Increase Survivability of Breast Cancer Patients

Abstract

Breast cancer is currently the second leading cause of cancer-related deaths and the most commonly diagnosed cancer among women in the United States. Localized breast cancer has a five-year survival rate of 99%, however the survival rate for patients with distant metastasis is 29%, despite improved screening and detection methods. Currently, there are few targeted therapies that specifically inhibit metastasis. Research performed by our lab and others has shown that inflammatory cytokines play a crucial role in promoting cancer growth and metastatic potential in cancer cells. While efforts have been made to develop FDA approved therapeutics for inflammatory cytokines, very few have successfully made it through clinical trials and several cytokines still lack effective clinical inhibitors. Our research has developed a stepwise approach towards designing and testing novel small molecule inhibitors (SMIs) against inflammatory cytokines. In silico computational screening of compound libraries towards specific inflammatory cytokines revealed potential molecules that interact with receptor binding regions and inhibit cytokine biological function. In vitro efficacy of the SMIs were analyzed with in silico and in vitro methods, SMI’s are structurally modified with effective functional groups to increase efficacy of binding interaction and reduce toxicity for living systems. Finally, small molecule inhibitors that have been sufficiently tested for efficacy are then examined in mice to evaluate toxicity and to analyze reduction of tumor growth metastases. Our interdisciplinary team has designed, synthesized, and tested small molecule inhibitors (SMIs) to target inflammatory cytokines shown to promote metastasis in cancer with the long-term goal of understanding lethal breast cancer metastasis, as well as providing a novel FDA approved therapeutic for breast cancer patients.