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Sotorasib, sold under the brand names Lumakras and Lumykras, is an anti-cancer medication used to treat non-small-cell lung cancer. [4] [5] It targets a specific mutation, G12C, in the protein K-Ras encoded by gene KRAS which is responsible for various forms of cancer. [7] [8] Sotorasib is an inhibitor of the RAS GTPase family. [4]
A phase Ia/Ib dose escalation trial of the oral selective KRAS G12C inhibitor divarasib was published in 2023, where the drug was tested in non-small cell lung cancer, colorectal cancer, and other solid tumors with KRAS G12C mutations. [55] It continues in phase I and II studies for several cancer types as of August 2023. [56] [57] [58] [59]
K-Ras(G12C) inhibitor 6 is an irreversible inhibitor of oncogenic K-Ras(G12C), subverting the native nucleotide preference to favour GDP over GTP. Its family of inhibitors allosterically control GTP affinity and effector interactions by fitting inside a "pocket", or binding site, of mutant K-Ras. It is the most frequently mutated oncogene. [1]
mRNA-5671 also known as V941 is a cancer vaccine candidate developed by Moderna. [1] It is a tetravalent vaccine that targets G12D, G12V, G13D or G12C driver mutations in the KRAS gene. [ 2 ] It is currently being evaluated for the treatment of either non-small cell lung cancer , colorectal cancers with microsatellite instability , or ...
Lewis lung carcinoma is a hypermutated Kras/Nras–mutant cancer with extensive regional mutation clusters in its genome. A tumor that spontaneously developed as an epidermoid carcinoma in the lung of a C57BL mouse. It was discovered in 1951 by Dr. Margaret Lewis of the Wistar Institute and became one of the first transplantable tumors. [1]
Approximately 98% of lung cancers are carcinoma, a term describing malignancies derived from transformed cells exhibiting characteristics of epithelium. About 2% of all lung cancers are non-carcinoma (mainly sarcoma, tumors of hematopoietic origin, or germ cell tumors. [5] These forms of lung cancer are usually treated differently from carcinomas.
MPE began as analysis of risk factors (e.g., smoking) and molecular pathological findings (e.g., KRAS G12C oncogene mutations in lung carcinoma). [ citation needed ] Studies to examine the relationship between an exposure and molecular pathological signatures of disease (particularly, cancer) became increasingly common throughout the 1990s and ...
The most common mutations are found at residue G12 in the P-loop and the catalytic residue Q61. The glycine to valine mutation at residue 12 renders the GTPase domain of Ras insensitive to inactivation by GAP and thus stuck in the "on state". Ras requires a GAP for inactivation as it is a relatively poor catalyst on its own, as opposed to other ...