Cited by 116Protein Kinase Regulation and GTPase SignalingLung Cancer Treatments and MutationsLung Cancer Research Studies

The genetics and biology of KRAS in lung cancer

Open access
Westcott, Peter M. K., To, Minh D.·2013·Chinese Journal of Cancer

Abstract

Mutational activation of KRAS is a common oncogenic event in lung cancer and other epithelial cancer types. Efforts to develop therapies that counteract the oncogenic effects of mutant KRAS have been largely unsuccessful, and cancers driven by mutant KRAS remain among the most refractory to available treatments. Studies undertaken over the past decades have produced a wealth of information regarding the clinical relevance of KRAS mutations in lung cancer. Mutant Kras-driven mouse models of cancer, together with cellular and molecular studies, have provided a deeper appreciation for the complex functions of KRAS in tumorigenesis. However, a much more thorough understanding of these complexities is needed before clinically effective therapies targeting mutant KRAS-driven cancers can be achieved.

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Crossref · 10.5732/cjc.012.10098

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  • The difficulty of drugging KRAS reflects picomolar RAS affinity for GTP, high intracellular GTP concentration of about 500 nM, and the absence of a deep or pharmacologically actionable small-molecule-binding pocket; GTP-competitive RAS inhibitors are therefore unfeasible.

    “The several-decade struggle to drug KRAS and other RAS isoforms25,61 reflects challenges posed by three key biochemical features: first, the picomolar affinity of RAS proteins for GTP62; second, the high intracellular concentrations of GTP (~500 nM)9; and third, the absence of a deep or pharmacologically actionable small-molecule-binding pocket in the RAS proteins.”

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Authors
Westcott, P. M. K., & To, M. D.
Affiliations
University of California, San Francisco (US)
Venue
Chinese Journal of Cancer
Published
2013-02-05
Volume
32
Issue
2
Pages
63-70
ISSN
  • 1000-467X (ISSN-L)
  • 1944-446X
OpenAlex
W1976566249
Cited by
116
References
78
Citations by year
2026: 7 · 2025: 18 · 2024: 8 · 2023: 9 · 2022: 14 · 2021: 15 · 2020: 14 · 2019: 8 · 2018: 8 · 2017: 3 · 2016: 4 · 2015: 5 · 2014: 2 · 2013: 1
FWCI
0.23
Type
journal article
Language
en
Open access
Locations
  • 癌症:英文版 (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
  • National Science Foundation
  • National Institutes of Health
  • University of California, San Francisco
  • National Institute of General Medical Sciences (T32GM007175)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
  • Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
Keywords
KRAS mutation, lung cancer, oncogenic KRAS, carcinogenesis, KRAS-targeted therapy, epithelial cancers, cancer genetics
MeSH terms
Animals, Carcinoma, Non-Small-Cell Lung, Cell Transformation, Neoplastic, Disease Susceptibility, Humans, Lung Neoplasms, Mutation, Neoplasms, Experimental, Proto-Oncogene Proteins, Genetic Therapy, Signal Transduction, Proto-Oncogene Proteins p21(ras), ras Proteins, RNA, Small Interfering, Mice, Gene Knockdown Techniques

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