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Ras history: The saga continues
Open accessAbstract
Although the roots of Ras sprouted from the rich history of retrovirus research, it was the discovery of mutationally activated RAS genes in human cancer in 1982 that stimulated an intensive research effort to understand Ras protein structure, biochemistry and biology. While the ultimate goal has been developing anti-Ras drugs for cancer treatment, discoveries from Ras have laid the foundation for three broad areas of science. First, they focused studies on the origins of cancer to the molecular level, with the subsequent discovery of genes mutated in cancer that now number in the thousands. Second, elucidation of the biochemical mechanisms by which Ras facilitates signal transduction established many of our fundamental concepts of how a normal cell orchestrates responses to extracellular cues. Third, Ras proteins are also founding members of a large superfamily of small GTPases that regulate all key cellular processes and established the versatile role of small GTP-binding proteins in biology. We highlight some of the key findings of the last 28 years.
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“KRAS has historically been considered ‘undruggable’ owing to a lack of pharmacologically targetable pockets within the mutant isoforms.”
From The current state of the art and future trends in RAS-targeted cancer therapies (2022) · cites this paper as [26]
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Metadata
- Authors
- Cox, A. D., & Der, C. J.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Venue
- Small GTPases
- Publisher
- Informa UK Limited
- Published
- 2010-07
- Volume
- 1
- Issue
- 1
- Pages
- 2-27
- ISSN
- 2154-1248 (ISSN-L)
- 2154-1256
- PMC
- PMC3109476
- OpenAlex
- W2333950962
- Cited by
- 706
- References
- 329
- Citations by year
- 2026: 19 · 2025: 39 · 2024: 48 · 2023: 43 · 2022: 78 · 2021: 59 · 2020: 71 · 2019: 70 · 2018: 43 · 2017: 40 · 2016: 44 · 2015: 49 · 2014: 30 · 2013: 34 · 2012: 21
- FWCI
- 9.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Small GTPases (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ca042978-30)
- National Cancer Institute (R01CA109550, R01-CA042978, P50CA106991, U19CA067771, R01CA127152)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- Ras, ras gene, oncogenic mutations, tumor origin, signal transduction, G proteins
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