RAS G12D is one of the most frequent mutations in RAS, and when it occurs, it leaves RAS in a permanently active state, causing the cell to proliferate uncontrollably. Examples of the so-called RAS-addicted cancers are colorectal cancer or pancreatic ductal adenocarcinoma.
Revolution Medicines Inc. has synthesized macrocyclic compounds acting as GTPase KRAS, NRAS, HRAS and their mutant inhibitors reported to be useful for the treatment of cancer.
The effective targeting of RAS-mutant acute myeloid leukemia (AML) still remains a challenge; RAS mutations are tied to relapse to targeted therapy, such as resistance to FLT3 inhibitors due to the RAS/MAPK pathway, for example.
The development of covalent KRAS G12C inhibitors has represented a significant advance for non-small-cell lung cancer treatment, but other mutations such as KRAS G13C/D still lack effective treatments.
The existence of two approved therapies, Lumakras (sotorasib, Amgen Inc.) and Karzati (adagrasib, Mirati Therapeutics Inc.), has been a triumphant success against KRAS, a protein that was once considered undruggable.
The existence of two approved therapies, Lumakras (sotorasib, Amgen Inc.) and Karzati (adagrasib, Mirati Therapeutics Inc.), has been a triumphant success against KRAS, a protein that was once considered undruggable. KRAS is the most frequently mutated oncogene in solid tumors. KRAS driver mutations are found in about 30% of non-small-cell lung cancers (NSCLC), about half of colorectal cancers, and more than 90% of pancreatic cancers. Lumakras and Karzati both target the G12C mutation. Inhibitors that target other mutations, like G12D, are now making their way through preclinical and clinical development, while some companies are developing therapies that would target mutated KRAS more broadly, irrespective of the specific mutation that is activating the protein.
Aethon Therapeutics Inc. has entered into a collaboration agreement with Revolution Medicines Inc. under which Aethon will use its Hapimmune platform to discover novel bispecific antibodies to mount an immune attack directed towards cancer cells hit by Revolution Medicines’ RAS(ON) inhibitors.
Revolution Medicines Inc. has divulged son of sevenless homolog 1 (SOS1) inhibitors reported to be useful for the treatment of cancer, neurofibromatosis type 1, cardiofaciocutaneous, Noonan, Costello and Legius syndrome (neurofibromatosis type 1-like syndrome), among others.
Researchers from Revolution Medicines Inc. presented the discovery and preclinical characterization of RMC-5127, a novel noncovalent, tri-complex inhibitor of GTPase KRAS (G12V mutant), or KRAS G12V(ON).
Revolution Medicines Inc. is acquiring Eqrx Inc. in an all-stock transaction designed to add more than $1 billion in net cash for Revolution so it can forge ahead with its RAS pathway programs. Serial biotech entrepreneur and investor Alexis Borisy co-founded Eqrx in 2020 to deliver new medicines for cancer and other conditions at "radically lower prices." Borisy also co-founded Revolution, where he remains as executive chairman.
