Transformation of Immunosuppressive mtKRAS Tumors Into Immunostimulatory Tumors by Nerofe and Doxorubicin


“[...] we demonstrated that the combination of Nerofe and DOX exerts a synergistic effect during mCRC treatment [...]”


BUFFALO, NY- July 5, 2023 – A new research paper was published in Oncotarget's Volume 14 on July 1, 2023, entitled, “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. Recently, two drugs that specifically target KRAS G12C, sotorasib (Lumakras™) and adagrasib (Krazati™), have received accelerated approval by the FDA for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC, who have received at least one prior systemic therapy. These drugs are the first RAS GTPase family inhibitors to be approved for clinical use, representing a major breakthrough in the field of precision oncology.


In this new study, researchers Joel Ohana, Uziel Sandler, Orly Devary, and Yoram Devary from Immune System Key (ISK) and Jerusalem College of Technology 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. 


“The objective of the present study was to investigate the synergistic effect of the combination of Nerofe and DOX in colorectal cancer and its underlying mechanism.”


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.


“In conclusion, we demonstrated that the combination of Nerofe and DOX exerts a synergistic effect during mCRC treatment, which could stem from several independent and complementary mechanisms of action.”


Read the full paper: DOI: https://doi.org/10.18632/oncotarget.28467 

Correspondence to: Yoram Devary


Email: [email protected] 


Keywords: Colorectal cancer, KRAS, apoptosis, hormone peptide, endoplasmic reticulum stress



About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open-access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.


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