Novel Molecular Biomarkers and Therapeutics for Colorectal Cancer

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PROJECT SUMMARY/ABSTRACT With an estimated 135,000 new cases and 50,000 deaths in 2017, colorectal cancer (CRC) is the second leading cause of cancer mortality in the United States. Thus, new approaches are needed to elucidate the biology of CRC, to identify individuals at high risk for CRC, to develop new and better targeted strategies for preventing CRC, and to develop new and better treatments. The Case gastrointestinal cancers Specialized Program of Research Excellence (GI SPORE) conducts an integrated spectrum of transdisciplinary human research particularly focusing on developing novel biomarkers and targeted therapies for colorectal and esophageal malignancies. Dr. Markowitz (Unit Director), a medical oncologist and a leading scientist nationally in translational research of CRC, is the PI of the Case GI SPORE. Dr. Stephen Fink (the Research Specialist) is a senior member of the Markowitz research group and an integral member of the Case GI SPORE. This proposal is based on the several high impact discoveries that Dr. Fink has made that have been key to the continued success of the Case GI SPORE, and outlines the active role Dr. Fink will play in achieving the goals of future studies in the program. Dr. Fink's studies are of particular relevance to SPORE Project 1, which centers on predictive, prognostic, and therapeutic applications of 15-Hydroxyprostaglandin dehydrogenase (15-PGDH). Additionally, Dr. Fink's expertise in leading up biomarker development has resulted in his recent discovery of CEMIP/KIAA1199 as a biomarker for detection and prognosis, and as a potential therapeutic target. These findings have opened up new research avenues within the Case GI SPORE. Goals: As a key Investigator in 15-PGDH studies, Dr. Fink will be directly involved in: i) Determining if low levels of 15-PGDH expression will identify individuals with increased CRC risk; ii) Determining if variation in 15-PGDH and/or other prostaglandin pathway genes identify individuals and cancers that will respond to aspirin chemoprevention; and iii) Identifying key regulators and effectors of colon 15-PGDH signaling. Furthermore, as the lead person directing a SPORE developmental project on CEMIP, Dr. Fink will direct research studies to: i) Develop translational applications of CEMIP for early detection and prognosis of CRC; and ii) Test if anti-CEMIP antibodies can block in vivo growth of tumors. Success of these studies will: i) help identify individuals in the general population who are at increased risk for CRC (15-PGDH studies); ii) provide new strategies for CRC chemoprevention and early detection (15-PGDH and CEMIP studies); and iii) provide a new therapeutic avenue for disease treatment (CEMIP studies). The Research Specialist award will provide support to enable Dr. Fink to develop new methodologies and techniques as well as help facilitate Dr. Fink's long-term goal of being a team scientist who provides expert guidance in discovery and development of biomarkers and therapeutic targets within the GI SPORE and the Case Cancer Center.