Laboratory and Basic Science Research Commons^™

Hypoxia Activated Prodrug And Anti-Angiogenic Therapy Cooperate To Treat Pancreatic Cancer But Elicit Immune Suppressive G-Mdsc Infiltration, Arthur Liu

Dissertations & Theses (Open Access)

We previously showed that the hypoxia-activated prodrug TH-302 (Evofosfamide) reduces intratumoral hypoxia through a tissue remodeling process, initiates tumor vasculature reorganization, and sensitizes aggressive, spontaneous murine models of prostate cancer to immune checkpoint blockade (ICB). In a clinical trial testing the combination of TH-302 with cytotoxic T-lymphocyte-associated protein (CTLA-4) blockade (NCT03098160) a subset of metastatic, ICB refractory patients showed prolonged progression free survival. While these studies highlight hypoxia as therapeutically tractable, we lack a complete understanding of the contribution of the tumor vasculature to hypoxia reduction therapy, as well as the downstream consequences of hypoxia reduction on the cellular composition …