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Abstract IA01: Modeling and understanding tumor biologic mechanisms

This presentation will highlight our use of mouse models to dissect molecular and cellular interactions in the tumor microenvironment, including (i) the illumination of the role of myeloid cells in driving immune suppression in prostate cancer, and the impact of combined MDSC-targeted and immune checkpoint blockade therapies in the treatment of metastatic castration-resistant prostate cancer; (ii) the generation and analysis of oncogenic Kras in an inducible colorectal cancer mouse model, revealing the role of IRF2 in the recruitment of myeloid cells into the tumor microenvironment and informing patient selection for more effective ICB therapy in CRC; (iii) the concept of “synthetic essentiality” (a means by which to target specific tumor-suppressor gene deficiencies in cancer), exemplified by the identification of the role of CHD1 in modulation of the tumor microenvironment in Pten-deficient prostate cancer; (iv) the discovery of a symbiotic interaction between glioma cell (LOX) and macrophage (SPP1) in PTEN-null glioma, as well as macrophage reprogramming in immune suppression in glioblastoma; and (v) the role of KRAS in cancer metabolism, in particular how the tumor microenvironment may support KRAS-directed cancer cell metabolism and provide a nonautonomous mechanism enabling escape from Kras-dependent tumor growth. These illustrative examples provide translational opportunities to improve cancer patient treatment and survival. Citation Format: Adam Boutin, Peiwen Chen, Prasenjit Dey, Pingping Hou, Wen-Ting Liao, Xin Lu, Haoqiang Ying, Di Zhao, Ronald A. DePinho. Modeling and understanding tumor biologic mechanisms [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr IA01.