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  1. Targeting KRAS in cancer | Nature Medicine

  2. The KRAS-G12C inhibitor: activity and resistance - Nature

  3. KRAS G12C Mutations in NSCLC: From Target to Resistance

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    Recent advances in medicinal chemistry have established inhibitors targeting KRAS (G12C), a mutation found in ∼13% of lung adenocarcinomas and, at a lower frequency, in other cancers.
    A better understanding of the role of KRAS and its different mutations has led to the development of specific small-molecule inhibitors able to target KRAS G12C, an oncogenic driver mutation in a number of cancers, including non-small cell lung cancer.
    By requiring the mutant cysteine residue for binding, inhbitors of the KRAS variant with a p.Gly12Cys alteration (hereafter, KRAS G12C) specifically target the mutant protein while sparing KRAS wild-type protein. Historically, it was thought that KRAS oncoproteins were constitutively activated, ‘locked’ in an on state.
    The KRAS p.G12C mutation occurs in 13% of non–small-cell lung cancers (NSCLCs) and in 1 to 3% of colorectal cancers and other cancers. Sotorasib is a small molecule that selectively and irreversibly targets KRAS G12C. We conducted a phase 1 trial of sotorasib in patients with advanced solid tumors harboring the KRAS p.G12C mutation.
  5. The path to the clinic: a comprehensive review on direct KRAS …

  6. KRAS G12C Inhibition with Sotorasib in Advanced Solid …

    Web20 sep. 2020 · Sotorasib is a small molecule that selectively and irreversibly targets KRAS G12C. Methods. We conducted a phase 1 trial of sotorasib in patients with advanced solid tumors harboring the KRAS...

  7. Acquired Resistance to KRAS G12C Inhibition in Cancer …

    Web23 jun. 2021 · Acquired Resistance to KRAS G12C Inhibition in Cancer. KRAS is one of the most commonly mutated oncogenes in cancer. The KRAS protein normally functions as a molecular switch that cycles...

  8. Targeting KRAS(G12C): From Inhibitory Mechanism to …

    WebTargeting KRAS (G12C): From Inhibitory Mechanism to Modulation of Antitumor Effects in Patients: Cell. Perspective | Volume 183, ISSUE 4, P850-859, November 12, 2020. Download Full Issue. Targeting KRAS

  9. Sotorasib is First KRAS Inhibitor Approved by FDA - NCI

    Web25 jun. 2021 · Sotorasib is the first KRAS inhibitor to treat NSCLC with the G12C mutation, which is common in smokers. The drug shrank tumors in 36% of patients and delayed disease progression for 7 months, but more …

  10. Distribution of KRAS G12C Somatic Mutations across …

    Web13 jan. 2021 · These data illustrate the presence of differences according to sex and ethnic group in the prevalence of KRASG12C mutations in various cancer types and emphasize the importance of mutation...

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