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KRAS: The Critical Driver and Therapeutic Target for Pancreatic Cancer
Open accessAbstract
mutation frequency, pancreatic ductal adenocarcinoma (PDAC) is considered the most RAS-addicted of all cancers. We review the role of KRAS as a driver and therapeutic target in PDAC.
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“This high prevalence is significant as it makes PDAC arguably the most RAS-addicted cancer, with substantial experimental evidence that mutant KRAS is essential for its growth [107].”
From Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer (2024) · cites this paper as [107]
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“In particular, the KRAS isoform is mutated in 84% of all RAS-mutant cancers, with a near 100% mutation frequency in PDAC.”
From Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer (2024) · cites this paper as [107]
In the citing paper
“The majority of KRAS mutations are at codon 12, with the highest prevalence of G12D mutation (35%), followed by G12V (20–30%), G12R (10–20%), Q61 (~5%), G12C (1–2%), and other rare muations9–12.”
From Impact of KRAS mutations and co-mutations on clinical outcomes in pancreatic ductal adenocarcinoma (2024) · cites this paper as [9]
In the citing paper
“In pancreatic cancer, KRAS mutation is often the initiating genetic event leading to pancreatic intraepithelial neoplasms. Carcinogenesis and metastasis are stimulated by acquiring other mutations such as p53 (64%), SMAD4 (21%), and CDKN2A (17%) [63].”
From Drugging KRAS: Current perspectives and state-of-art review (2022) · cites this paper as [63]
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“A number of highly selective and potent inhibitors have been developed against kinases in the Ras signaling network particularly those in the MAPK and PI3K/mTOR pathways (9, 12).”
From KRAS mutation in pancreatic cancer (2021) · cites this paper as [12]
In the citing paper
“the KRASG12C allele occurs in only 1.6% of PDAC cases, whereas the KRASG12D allele is present in greater than 40%, followed in frequency by KRASG12V and KRASG12R mutations74.”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [74]
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“Further, wholeexome deep-sequencing data of pancreatic cancer patients shows that 93% of the rare PIK3CA mutations co-occur with aKRASmutation, suggesting activated KRAS alone is not sufficient to effectively activate PI3K (Jones et al. 2008; Biankin et al. 2012; Sausen et al. 2015; Waddell et al. 2015; Witkiewicz et…”
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Metadata
- Authors
- Waters, A. M., & Der, C. J.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Venue
- Cold Spring Harbor Perspectives in Medicine
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2017-12-11
- Volume
- 8
- Issue
- 9
- Pages
- a031435
- ISSN
- 2157-1422 (ISSN-L)
- PMC
- PMC5995645
- OpenAlex
- W2771729549
- Cited by
- 875
- References
- 109
- Citations by year
- 2026: 73 · 2025: 112 · 2024: 121 · 2023: 118 · 2022: 153 · 2021: 157 · 2020: 98 · 2019: 35 · 2018: 8
- Type
- posted content
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cold Spring Harbor Perspectives in Medicine (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- Funders
- U.S. Department of Defense
- American Association for Cancer Research
- Pancreatic Cancer Action Network
- Lustgarten Foundation
- National Science Council
- National Institutes of Health (5r01ca042978-30)
- National Cancer Institute (CA042978, CA203657, P01CA203657, R01CA175747, T32CA009156, P50CA196510, R01-CA042978, CA199235, U01CA199235, CA196510, P30CA016086)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- KRAS, pancreatic ductal adenocarcinoma, pancreatic cancer, driver mutations, therapeutic target, KRAS inhibitors
- MeSH terms
- Adenocarcinoma, Animals, Humans, Mutation, Signal Transduction, Proto-Oncogene Proteins p21(ras), Carcinoma, Pancreatic Ductal, Protein Kinase Inhibitors, Molecular Targeted Therapy
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