US, China Biotechs Report Promising Results in Cancer Research for mTORC1 and IN10018
It's been a week of promising news for cancer research, with two possible treatment modalities reporting positive results.
California-based Revolution Medicines announced in a press release that it has published its original scientific paper on the anti-tumor effects of bi-steric mTORC1-selective inhibitors that can possibly suppress phosphorylation 4EBP1, which is a key translational regulator of oncogene expression.
The study, which now appears on Nature Chemical Biology, highlights the potential of MTORC1 in treating tumors caused by genomic activations of its pathway.
The results thus far strengthen observations from Revolution Medicines' recently started RMC-5552 clinical development program. RMC-5552 is a selective and potent mTORC1 inhibitor that's being developed to treat cancer patients with solid tumors that have hyperactivated mTOR pathways and for some with RAS-addicted cancers. The component has repeatedly shown promise in several earlier preclinical tests, with one of the models suggesting that it could be used for lung cancer cases when combined with KRASG12C inhibitors.
“The published research details the manner in which these selective inhibitors of mTORC1 potently inhibit tumor growth while causing less toxicity and receptor reactivation, a potential mechanism of adaptive resistance, as compared to conventional mTOR inhibitors. These study results offer compelling rationale for our recently initiated clinical development program for RMC-5552,” said Steve Kelsey M.D., president of research and development at Revolution Medicines.
The paper is titled "Selective Inhibitors of mTORC1 activate 4eBP1 and supper tumor growth.”
Meanwhile, Shanghai-based biotechnology company InxMed Co announced that it has published a study on the effect of the combination of KRAS G12C inhibition and the FAK inhibitor IN10018 in creating anticancer effects in several in vivo and in vitro models. The combo was also observed to help improve treatment outcomes by reducing the extent of drug resistance. FAK, a downstream KRAS target, has been linked to drug resistance of chemotherapies and other targeted treatments.
InxMed owns the exclusive global rights to develop and commercialize IN10018 (previously tagged as BI853520). Early results from clinical studies have shown that it can overcome immune tolerance and fibrotic barriers and eventually enhance multi-modalities of treatment, including chemotherapy, radiation therapy, targeted therapy, and immune therapy.
Though based in China, InxMed has been building translation medicine and clinical development teams globally, covering Beijing, Canada, Australia, and the U.S. The company focuses its research on tumor resistance and metastasis, particularly on developing a new drug on anti-PD-1/PD-L1 treatment resistance.
In a press release, InxMed chairman and chief executive Dr. Zaiqi Wang said that FAK inhibitor 1N10018 had exhibited antitumor effects and positive safety tolerance across clinical trials conducted in Australia, China, and the U.S. He also said that, given the potential presented, InxMed will continue to pursue its translational medicine research and clinical trial efforts, with the goal to create efficient treatment options.
The paper is titled "Focal Adhesion Kinase (FAK) Inhibition Synergizes with KRAS G12C Inhibitors in Treating Cancer through the Regulation of the FAK–YAP Signaling" and is published on Advanced Science. It was written in collaboration with Ruijin Hospital, Shanghai Jiaotong University School of Medicine.