Abstract
Abstract Metastasis-associate protein 1 (MTA1), a master transcriptional co-regulator and chromatin modifier, is strongly associated with clinically aggressive prostate cancer. The loss of MTA1 reduces the aggressiveness and metastatic potential of prostate cancer cells. Preclinical studies with subcutaneous and orthotopic MTA1 knockdown xenograft models have shown the tumor promoting role of MTA1 and associated survival pathways in prostate cancer. However, the exact role of MTA1 in the pathobiology of prostate cancer is unknown. We first generated a conditional mouse with human MTA1 transgene knocked into the mouse Rosa26 locus (R26MTA1; Cre+ ). By crossing a R26MTA1 mouse with a Pten “floxed” mouse, we have created unique high-risk high-grade PIN-prone R26MTA1; Ptenf/+; Cre+ mice and a high-risk R26MTA1; Ptenf/f; Cre+ cohort of mice with characteristics of a castrate-resistant neuroendocrine subtype suitable for early chemoprevention/interception and novel effective therapies, respectively. I will discuss the potent MTA1-targeted anticancer effects of natural stilbenes (resveratrol, pterostilbene, and Gnetin C) observed in the preclinical R26MTA1; Ptenf/+; Cre+ model mimicking high-risk premalignant tumors with overexpressed MTA1. Further, evidence will be provided on the role of MTA1 in castrate resistance and on the neuroendocrine features defining the potential of the R26MTA1; Ptenf/f; Cre+ model in discovering novel chemoimmunotherapies. Our studies demonstrate progress towards successful targeted interception strategies for prostate cancer with an implication for precision medicine. Supported by the NCI/NIH R15CA216070 Award. Citation Format: Anait S. Levenson. Unique mouse models of high-risk prostate cancer adequate for targeted interception [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr A072.
Published Version
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