Pancreatic ductal adenocarcinoma (PDAC) is still a highly lethal cancer with limited therapeutic options. Its lethality mainly stems from activating KRAS mutations and a metabolic dependence on nicotinamide adenine dinucleotide (NAD). Researchers from Remedy Plan Inc. have presented data on RPT-E-037, which exerts dual targeting of NAD metabolism through Nampt inhibition and KRAS signaling inhibition using a pan-RAS inhibitor (RMC-6236).
Kestrel Therapeutics Inc. has obtained IND approval from the FDA for KST-6051, an oral, small-molecule pan-KRAS inhibitor being developed for the treatment of KRAS-driven cancers.
Mutant KRAS is a well-known oncogenic driver and has remained undruggable for many decades. The development of pan-KRAS inhibitors that target a broad range of mutations is a promising approach to cancer treatment.
RAS is the most mutated oncogene in cancer (about 30% rate), where mutations in KRAS are the most prevalent. The approval of covalent KRAS G12C inhibitors has shown allosteric inhibition of KRAS to be a feasible therapeutic strategy, and there is interest in developing new KRAS-directed therapies to target additional KRAS mutants. Amgen has presented data regarding its pan-KRAS inhibitor AMG-410.
Mutations in the GTPase KRAS drive proliferation of many types of tumors, and daraxonrasib (RMC-6236), which inhibits various KRAS mutants, can slow growth of pancreatic and lung cancers. Researchers at City University of New York and Weill Cornell Medical College have demonstrated that it also showed effects in osteosarcoma models expressing mutated KRAS.
Erasca Inc. has obtained IND clearance by the FDA for ERAS-4001, an oral selective pan-KRAS inhibitor, for the treatment of patients with KRAS-mutant solid tumors.
A Merck Sharp & Dohme LLC patent details new GTPase KRAS and its G12C, G12D, G12V and/or G13D mutant inhibitors reported to be useful for the treatment of cancer.
Suzhou Zion Pharma Technology Co. Ltd. has identified GTPase KRAS G12D or G13D mutant and/or KRAS inhibitors reported to be useful for the treatment of cancer.
Quanta Therapeutics Inc. has gained IND clearance from the FDA for QTX-3544, an oral multi-KRAS inhibitor with G12V-preferring activity and dual ON/OFF state.
Pancreatic ductal adenocarcinoma (PDAC) has a low 5-year survival rate of <12%. Even though KRAS is mutated in about 88% of PDACs, the KRAS G12C mutation is rare, limiting the use of KRAS G12C inhibitors. Hence, there is a need for pan-RAS inhibitors to cover the broad RAS mutation spectrum in PDAC.
