Transformation of immunosuppressive mtKRAS tumors into immunostimulatory tumors by Nerofe and Doxorubicin

Members of the rat sarcoma viral oncogene (Ras) subfamily KRAS are frequently mutated oncogenes in human cancers and have been identified in pancreatic ductal, colorectal, and lung adenocarcinomas. In this study, we show that a derivative of the hormone peptide Tumor Cell Apoptosis Factor (TCApF), Nerofe^™ (dTCApFs), in combination with Doxorubicin (DOX) substantially reduces viability of tumor cells. It was observed that the combination of Nerofe and DOX downregulated KRAS signaling via miR217 upregulation, resulting in enhanced Apoptosis of tumor cells. In addition, the combination of Nerofe and DOX also resulted in activation of the immune system against tumor cells, manifested by an increase in the immunostimulatory cytokines IL-2 and IFN-γ as well as the recruitment of NK cells and M1 macrophages to the tumor site.

Colorectal cancer; KRAS; apoptosis; endoplasmic reticulum stress; hormone peptide.