RAS mutations in human cancers: Roles in precision medicine

Ras proteins play a crucial role as a central component of the cellular networks controlling a variety of signaling pathways that regulate growth, proliferation, survival, differentiation, adhesion, cytoskeletal rearrangements and motility of a cell. Almost, 4 decades passed since Ras research was s...

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Bibliographic Details
Published in:Seminars in cancer biology 2019-12, Vol.59, p.23-35
Main Authors: Murugan, Avaniyapuram Kannan, Grieco, Michele, Tsuchida, Nobuo
Format: Article
Language:English
Subjects:
Alleles
Biomarkers, Tumor
Cancer
Cell Transformation, Neoplastic - genetics
Gene Expression Regulation, Neoplastic
Gene Frequency
Genes, ras
Genetic Association Studies - methods
Genetic Predisposition to Disease
HRAS
Humans
KRAS
Molecular Targeted Therapy
Mutation
Neoplasms - diagnosis
Neoplasms - genetics
Neoplasms - therapy
NRAS
Oncogene
Personalized medicine
Precision medicine
Precision Medicine - methods
Signal Transduction
Structure-Activity Relationship
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Summary:Ras proteins play a crucial role as a central component of the cellular networks controlling a variety of signaling pathways that regulate growth, proliferation, survival, differentiation, adhesion, cytoskeletal rearrangements and motility of a cell. Almost, 4 decades passed since Ras research was started and ras genes were originally discovered as retroviral oncogenes. Later on, mutations of the human RAS genes were linked to tumorigenesis. Genetic analyses found that RAS is one of the most deregulated oncogenes in human cancers. In this review, we summarize the pioneering works which allowed the discovery of RAS oncogenes, the finding of frequent mutations of RAS in various human cancers, the role of these mutations in tumorigenesis and mutation-activated signaling networks. We further describe the importance of RAS mutations in personalized or precision medicine particularly in molecular targeted therapy, as well as their use as diagnostic and prognostic markers as therapeutic determinants in human cancers.
ISSN:1044-579X
1096-3650
DOI:10.1016/j.semcancer.2019.06.007