» Articles » PMID: 39654099

Role of Silent Mutations in KRAS -mutant Tumors

Overview
Specialty General Medicine
Date 2024 Dec 10
PMID 39654099
Authors
Affiliations
Soon will be listed here.
Abstract

Silent mutations within the RAS  gene have garnered increasing attention for their potential roles in tumorigenesis and therapeutic strategies. Kirsten-RAS ( KRAS ) mutations, predominantly oncogenic, are pivotal drivers in various cancers. While extensive research has elucidated the molecular mechanisms and biological consequences of active KRAS  mutations, the functional significance of silent mutations remains relatively understudied. This review synthesizes current knowledge on KRAS  silent mutations, highlighting their impact on cancer development. Silent mutations, which do not alter protein sequences but can affect RNA stability and translational efficiency, pose intriguing questions regarding their contribution to tumor biology. Understanding these mutations is crucial for comprehensively unraveling KRAS -driven oncogenesis and exploring novel therapeutic avenues. Moreover, investigations into the clinical implications of silent mutations in KRAS -mutant tumors suggest potential diagnostic and therapeutic strategies. Despite being in early stages, research on KRAS  silent mutations holds promise for uncovering novel insights that could inform personalized cancer treatments. In conclusion, this review underscores the evolving landscape of KRAS  silent mutations, advocating for further exploration to bridge fundamental biology with clinical applications in oncology.

References
1.
Pylayeva-Gupta Y, Grabocka E, Bar-Sagi D . RAS oncogenes: weaving a tumorigenic web. Nat Rev Cancer. 2011; 11(11):761-74. PMC: 3632399. DOI: 10.1038/nrc3106. View

2.
Kimchi-Sarfaty C, Oh J, Kim I, Sauna Z, Calcagno A, Ambudkar S . A "silent" polymorphism in the MDR1 gene changes substrate specificity. Science. 2006; 315(5811):525-8. DOI: 10.1126/science.1135308. View

3.
. Pan-cancer analysis of whole genomes. Nature. 2020; 578(7793):82-93. PMC: 7025898. DOI: 10.1038/s41586-020-1969-6. View

4.
Katti A, Diaz B, Caragine C, Sanjana N, Dow L . CRISPR in cancer biology and therapy. Nat Rev Cancer. 2022; 22(5):259-279. DOI: 10.1038/s41568-022-00441-w. View

5.
Linnane E, Davey P, Zhang P, Puri S, Edbrooke M, Chiarparin E . Differential uptake, kinetics and mechanisms of intracellular trafficking of next-generation antisense oligonucleotides across human cancer cell lines. Nucleic Acids Res. 2019; 47(9):4375-4392. PMC: 6511877. DOI: 10.1093/nar/gkz214. View