Blood vessels undergo rapid functional and structural changes called angiogenesis and vascular remodeling in many malignant disorders. Although previous genetic and molecular studies have identified the significance of vascular changes in pathologic conditions including cancer, major challenges are 1) to efficiently target vascular changes in tumor microenvironment during tumor progression, leading to effective anti-tumor and anti-metastatic effects and 2) to determine a potential interplay between the vascular changes and immune system in cancer.
We are currently examining two inter-related topics:
- To understand the significance of vascular niche on promoting distant metastasis in pancreatic neuroendocrine tumors in relation to anti-VEGF therapy resistance.
- To identify the molecular mechanisms by which vascular abnormalities regulate immunosuppression and resistance to immunotherapy in cancer.
By using an integrated approach that combines cell biology with preclinical studies utilizing a genetically engineered mouse tumor model along with translational studies, our study will provide paths forward for the development of new therapeutic targets and of better therapeutic strategies in cancer promoting vascular normalization and effective anti-tumor effects.