Entrepreneurial Sciences in Cancer Awardees

2022 Awardees

Philip Howe, Ph.D.

Professor, Department of Biochemistry and Molecular Biology

Project: Small Molecule Inhibitor of ARIH1

Co-Investigators: Breege Howley, Ph.D., and Yuri Peterson, Ph.D.

Dr. Howe's award is funded in part by LOWVELO, MUSC Hollings Cancer Center's fundraising bike ride that channels 100% of rider-raised dollars into cancer research.

Chemotherapy is the standard of care in metastatic triple negative breast cancer (TNBC). Unfortunately, this treatment strategy results in low rates of complete response and the development of recurrent disease. Therefore, there is an urgent need for therapies that can improve TNBC patient outcomes. We have delineated a novel role for ARIH1, an E3 ubiquitin ligase, in tumor progression of TNBC. We found that silencing of ARIH1 in TNBC cells reduces cell invasion and cancer cell stemness that are important for metastasis. Additionally, we and others have shown a role for ARIH1 in chemotherapeutic response. We see increased cell killing in response to the chemotherapeutics paclitaxel and doxorubicin in TNBC cells when ARIH1 is silenced.

To develop an inhibitor of ARIH1 function, we identified small molecules from the South Carolina Compound Collection (SC3) that disrupt ARIH1 activity. Hit compounds from our screen can inhibit ARIH1 function in vitro, phenocopy the inhibitory effects of ARIH1 silencing on cancer stemness and improve chemo-response in TNBC cells. Entrepreneurial Sciences in Cancer funding has allowed us to pursue objectives that are crucial for the preclinical development of our novel therapeutics.

John Wrangle, M.D.

Associate Professor, Department of Medicine

Project: Targeting Tumoral Tissue Factor with a Novel Rationally Designed Bispecific-Antibody Strategy

Co-Investigator: Alessandra Metelli, Ph.D.

Dr. Wrangle's award is funded in part by LOWVELO, MUSC Hollings Cancer Center's fundraising bike ride that channels 100% of rider-raised dollars into cancer research.

Tumors are wounds which do not heal: growing and spreading tumors damage surrounding tissues and attract platelets on their surface. One way that tumor cells attract platelets is by making a protein called Tissue Factor. When platelets are in the tumor they promote tumor growth and spread by feeding cancer cells with growing factors, especially TGFβ. To stop this process, we have designed a two-arm therapy which blocks both Tissue Factor on cancer cells and TGFβ released by platelets.

This therapy is modeled on other drugs for very different targets, but are strategies which have shown promising activity. Unlike previous anti-platelet therapies, this antibody will not stop normal platelet function, so patients are not expected to experience bleeding events. Once we have generated our antibody we propose to study its anti-tumor effect in tumor animal models first, and upon safe and successful results, to test its anti-cancer effects in patients. Based on our unique approach to Tissue Factor antibody design and on our scientific and clinical expertise, we expect our anti-TF/TGFBR2 TRAP antibody to be well-tolerated and to have promising clinical activity potential for cancer patients.