SPORE in Gastrointestinal Cancer
The National Cancer Institute designed Specialized Programs of Research Excellence (SPOREs) to translate novel scientific discoveries into clinical testing or trials for the treatment of cancer. Vanderbilt-Ingram Cancer Center has a SPORE focused on the treatment of gastrointestinal cancer.
Overview
The Vanderbilt-Ingram Cancer Center (VICC) SPORE in Gastrointestinal Cancer supports three research projects aimed at addressing questions of importance in human GI cancer. All projects are translational, multidisciplinary, and led by co-investigators from multiple departments across Vanderbilt University School of Medicine with complementary basic science and translational/clinical expertise.
The VICC SPORE in GI Cancer supports three projects that focus on colorectal cancer, the second leading cause of cancer deaths in the United States. We aim for practice-changing approaches to the diagnosis and treatment of colorectal cancer.
GI SPORE Leadership
Robert Coffey, MD
Ingram Professor of Cancer Research
Project 1: Overcoming Immune Exclusion in Microsatellite Stable Colorectal Cancer
Jordan Berlin (Clinical Co-Leader)
Robert Coffey (Basic Co-Leader)
Ken Lau (Basic Co-Leader)
Aims: Although immune checkpoint inhibitors (ICIs) are highly effective in microsatellite unstable (MSI-H) colorectal cancer (CRC), it has a limited clinical benefit for the 85% of CRCs that are classified as microsatellite stable (MSS). This is due, at least in part, to a paucity of CD8+ T cells present in these tumors. The aim of Project 1 is to overcome this lack of intratumoral CD8+ T cells, which we use as our definition of immune exclusion (IEX), in MSS CRC.
Project 2: Targeting MYC in Colorectal Cancer
Kristen Ciombor (Clinical Co-Leader)
William Tansey (Basic Co-Leader)
Goals: The goal of Project 2 is to develop a new targeted therapy to treat colorectal cancer (CRC) by selectively inhibiting the ability of the MYC oncoprotein transcription factor to enhance ribosomal protein gene (RPG) expression. MYC is frequently dysregulated in CRC and is considered a highly validated target for treatment of a broad range of malignancies. Completion of this project will result in the first-in-class trial of a new therapy for patients with metastatic CRC for which there are currently limited treatment options.
Project 3: Characterization of Beta-Catenin Degraders for the Treatment of Colorectal Cancer
Cathy Eng (Clinical Co-Leader)
Stephen Fesik (Basic Co-Leader)
Ethan Lee (Basic Co-Leader)
Vivian Weiss (Basic Co-Leader)
Goals: The long-term objective of this study is to investigate how a new class of compounds, β-catenin degraders, can be exploited to target Wnt/ β-catenin (henceforth Wnt)-driven colorectal cancers (CRCs). Aberrant activation of the Wnt pathway drives the initiation and progression of nearly all CRCs. To date, no drugs inhibiting the Wnt pathway have been FDA-approved due to a lack of druggable targets that can bypass common Wnt pathway mutations in CRC.
Featured Images from GI SPORE research
