Abstract P68: Novel biologic peptide shows potent anti-cancer activity as a sole therapy and in combination with cobimetinib in colon cancer models

A novel biologic peptide (NBP) showed anti-cancer mechanisms with tumor specific cytotoxicity leading to cancer cell death. It affects downstream G2/M signalling pathway leading to suppression of cell survival, growth and proliferation. In this study, we pursued to further characterize the anti-tumor activity of NBP in HCT116 xenografts in athymic mice. Since inflammation and mast cells are associated with colon cancer progression, we examined the effect of NBP treatment on number of mast cells in tumors which were significantly reduced in comparison to the tumor sections of untreated groups. NBP treatment in athymic nude mice with colon tumors (induced by HCT116 cells) had reduced tumor weights and tumor volume compared to control (vehicle-treated) mice. Further, NBP reduces expression levels of Ki-67 and Top2a genes, that are involved in the cell proliferation and G2/M transition. Furthermore, NBP in combination with cobimetinib showed significant tumor growth reduction in both tumor volumes and weight parameters. In vitro and in vivo assays suggested anti-tumorigenic potential of NBP and its combination with cobimetinib in comparison to their respective untreated controls. RNA sequencing data revealed genes involved in cell proliferation, inflammation, angiogenesis and epithelial mesenchymal transition were downregulated. Also, markers associated with colon cancer tumor growth and progression were targeted by NBP and cobimetinib either alone or in combination treatment. Overall, current findings in the study postulate scientific rationale to further explore NBP in colon cancer patients as a solo therapy or in combination with cobimetinib. Citation Format: Sivapriya Pavuluri and Sangita Mukhopadhyay. Novel biologic peptide shows potent anti-cancer activity as a sole therapy and in combination with cobimetinib in colon cancer models [abstract]. In: Proceedings of Frontiers in Cancer Science 2024; 2024 Nov 13-15; Singapore. Philadelphia (PA): AACR; Cancer Res 2025;85(15_Suppl):Abstract nr P68.