Abstract 6777: An ex-vivo organotypic culture platform of mucinous carcinomatosis peritonei identifies CDK4-6 inhibition as a novel treatment

Abstract Concomitant mutations in KRAS and GNAS have been linked to mucinous histology in gastrointestinal neoplasms of the appendix, colon, and pancreas (IPMN). Upon progression, these tumors are characterized by metastasis which favors the peritoneal surface, resulting in mucinous carcinomatosis peritonei (MCP). Recently we have described a novel technique which allows for long term culture and drug intervention of human MCP tumors ex-vivo. With evidence of durable clinical benefit of CDK4-6 inhibition in a single patient with chemo refractory MCP of appendiceal origin, we sought to further investigate anti-tumor responses using CDK4-6 inhibition in ex-vivo tumor slices, in order to identify candidates for a personalized clinical therapy trial. Here, in a comparison of ex-vivo patient tumor slices from 18 individual donors, treatment using CDK4-6 inhibitors revealed a significant reduction in cancer cell specific proliferation in mucinous GNAS-mut tumors compared to non-mucinous cancers. Anti-tumor responses of CDK4-6 were determined to be tumor-cell intrinsic, as CDK4-6 inhibition blocked proliferation of stromal cells in the TME independently of patient tumor mutational and mucin status. Based on these finding a personalized clinical trial was conducted where we report that 13 of 16 patients (81%) enrolled with MCP treated with palbociclib had at least a 10% decrease in CEA, as compared to historical chemotherapy responses rates reported from 14-30%. These results indicate that CDK4/6 inhibition is a novel and efficacious treatment for patients with MCP. Citation Format: Jonathan Weitz, Daisuke Nishizaki, Jay Patel, Isabella Ng, Siming Sun, Dana Ramms, Jingjing Zou, Joel Baumgartner, Kaitlyn Kelly, Hitendra Patel, Rebekah White, Jula Veerapong, Peter Vu, Silvio Gutkind, Herve Tiriac, Shumei Kato, Andrew Lowy. An ex-vivo organotypic culture platform of mucinous carcinomatosis peritonei identifies CDK4-6 inhibition as a novel treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6777.