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@ARTICLE{Isermann:296069,
      author       = {T. Isermann$^*$ and C. Sers$^*$ and C. J. Der and B.
                      Papke$^*$},
      title        = {{KRAS} inhibitors: resistance drivers and combinatorial
                      strategies.},
      journal      = {Trends in cancer},
      volume       = {11},
      number       = {2},
      issn         = {2405-8033},
      address      = {Amsterdam},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2025-00017},
      pages        = {91-116},
      year         = {2025},
      note         = {2025 Feb;11(2):91-116},
      abstract     = {In 1982, the RAS genes HRAS and KRAS were discovered as the
                      first human cancer genes, with KRAS later identified as one
                      of the most frequently mutated oncogenes. Yet, it took
                      nearly 40 years to develop clinically effective inhibitors
                      for RAS-mutant cancers. The discovery in 2013 by Shokat and
                      colleagues of a druggable pocket in KRAS paved the way to
                      FDA approval of the first covalently binding KRASG12C
                      inhibitors, sotorasib and adagrasib, in 2021 and 2022,
                      respectively. However, rather than marking the end of a
                      successful assault on the Mount Everest of cancer research,
                      this landmark only revealed new challenges in RAS drug
                      discovery. In this review, we highlight the progress on
                      defining resistance mechanisms and developing combination
                      treatment strategies to improve patient responses to KRAS
                      therapies.},
      subtyp        = {Review Article},
      keywords     = {KRAS (Other) / colorectal carcinoma (Other) / drug
                      resistance (Other) / non-small cell lung cancer (Other) /
                      pancreatic ductal adenocarcinoma (Other)},
      cin          = {BE01},
      ddc          = {610},
      cid          = {I:(DE-He78)BE01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39732595},
      doi          = {10.1016/j.trecan.2024.11.009},
      url          = {https://inrepo02.dkfz.de/record/296069},
}