We interrogate crosstalks between cancer cells and the microenvironment in metastatic colorectal and pancreatic cancers. For example, the surrounding liver mcrienvironment secretes soluble factors to activate HER3 and other survival pathways in cancer liver metastases. By identifying key survival pathways (such as HER3) ivolved in the crosstalk, we aim to develop therapeutic strategies of disrupting the crosstalk (e.g. block secreted factors, or block HER3 in cancer cells) to inhibit metastatic tumor outgrowth and, and also sensitize cancer cells to standard-of-care treatments for combination therapies.
Our laboratory aims to understand how the microenvironment mediates cancer cell growth and chemoresistance in colorectal and pancreatic cancers. We established strategies for isolating different cell types from malignant and non-malignant tissues (human and murine) as our working models to identify and validate new targets for developing new anti-neoplastic regimens.
With a focus on metastatic tumors in the liver, we determined that liver endothelial cells (ECs, represent over 50% of stromal cells in the liver) promote cancer cell survival by secreting soluble factors in a paracrine fashion (angiocrine). We also determined that HER3 (also known as ERBB3) is one of the major mediators of the EC-induced cancer cell survival and is potentially activated via a previously unknown mechanism (independent of other HER receptors and the identified HER3 ligands neuregulins).
- Determine the mechanism of EC-induced HER3 activation (EC-secreted new HER3 ligands)
- Characterize roles of liver ECs on cancer cell growth, response to chemotherapy, metabolism, and other pro-survival pathways.
- How other stromal cells in the microenvironment affect cancer cell functions
- Cancer-stromal cross-talk.