Matches in SemOpenAlex for { <https://semopenalex.org/work/W4307201601> ?p ?o ?g. }
- W4307201601 abstract "Abstract After decades of efforts, we have recently made progress into targeting KRAS mutations in several malignancies. Known as the ‘holy grail’ of targeted cancer therapies, KRAS is the most frequently mutated oncogene in human malignancies. Under normal conditions, KRAS shuttles between the GDP-bound ‘off’ state and the GTP-bound ‘on’ state. Mutant KRAS is constitutively activated and leads to persistent downstream signaling and oncogenesis. In 2013, improved understanding of KRAS biology and newer drug designing technologies led to the crucial discovery of a cysteine drug-binding pocket in GDP-bound mutant KRAS G12C protein. Covalent inhibitors that block mutant KRAS G12C were successfully developed and sotorasib was the first KRAS G12C inhibitor to be approved, with several more in the pipeline. Simultaneously, effects of KRAS mutations on tumour microenvironment were also discovered, partly owing to the universal use of immune checkpoint inhibitors. In this review, we discuss the discovery, biology, and function of KRAS in human malignancies. We also discuss the relationship between KRAS mutations and the tumour microenvironment, and therapeutic strategies to target KRAS. Finally, we review the current clinical evidence and ongoing clinical trials of novel agents targeting KRAS and shine light on resistance pathways known so far." @default.
- W4307201601 created "2022-10-30" @default.
- W4307201601 creator A5033351253 @default.
- W4307201601 creator A5043675371 @default.
- W4307201601 creator A5043871151 @default.
- W4307201601 creator A5055560185 @default.
- W4307201601 creator A5057105147 @default.
- W4307201601 creator A5062968216 @default.
- W4307201601 creator A5078137308 @default.
- W4307201601 date "2022-10-25" @default.
- W4307201601 modified "2023-10-14" @default.
- W4307201601 title "Drugging KRAS: current perspectives and state-of-art review" @default.
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