Paracrine Role of Endothelial Cells in HER3-Mediated Colon Cancer Cell Survival
Abstract
Colorectal cancer (CRC) remains the second-leading cause of cancer-related death in the United States and is the third most common cancer in the US military population. There are 10 available drugs for the treatment of patients with metastatic CRC (mCRC, spread of CRC). However, the duration of the effectiveness of therapy is typically less than 1 year and drug resistance is inevitable, leading to the death of most patients within ~2.5 years. The overall goal of this project is to identify novel therapeutic targets for the development of new treatments with the goal to improve the outcomes of patients with mCRC. In the past decade, preclinical studies demonstrated that endothelial cells (ECs), cells that line the interior surface of blood vessels, secret factors to promote cancer cell growth and resistance to chemotherapy in various cancer types. Our preliminary studies showed that ECs secreted factors to increase CRC cell viability and resistance to chemotherapy by activating the CRC cell surface receptor human epidermal growth factor receptor 3 (HER3, also known as ERBB3). We hypothesize that CRC-associated HER3 mediates the EC effects on promoting CRC cell growth and resistance to chemotherapy. Our proposed studies will determine a new role for ECs in mediating CRC cell growth and resistance to chemotherapy. We will also identify and validate factors secreted by ECs that are responsible for HER3 activation and cell survival in CRC cells. These studies will help us to understand how ECs mediate CRC cell growth and resistance to chemotherapy. This project will potentially lead to the development of novel therapies for patients with mCRC utilizing drugs targeting HER3 (HER3-targeted agents are already being assessed in clinical trials for various cancer types). Moreover, identification of key secreted factors from ECs will help to develop novel therapies for patients with mCRC.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810405
Entities
People
- Lee M. Ellis
Organizations
- United States Army
- University of Texas at Austin