1. Targeting Aberrant RAS/RAF/MEK/ERK Signaling for Cancer Therapy.
- Author
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Degirmenci U, Wang M, and Hu J
- Subjects
- Animals, Humans, Mitogen-Activated Protein Kinase Kinases metabolism, Neoplasms metabolism, raf Kinases metabolism, ras Proteins metabolism, Antineoplastic Agents pharmacology, Enzyme Inhibitors pharmacology, Mitogen-Activated Protein Kinase Kinases antagonists & inhibitors, Neoplasms drug therapy, Signal Transduction drug effects, raf Kinases antagonists & inhibitors, ras Proteins antagonists & inhibitors
- Abstract
The RAS/RAF/MEK/ERK (MAPK) signaling cascade is essential for cell inter- and intra-cellular communication, which regulates fundamental cell functions such as growth, survival, and differentiation. The MAPK pathway also integrates signals from complex intracellular networks in performing cellular functions. Despite the initial discovery of the core elements of the MAPK pathways nearly four decades ago, additional findings continue to make a thorough understanding of the molecular mechanisms involved in the regulation of this pathway challenging. Considerable effort has been focused on the regulation of RAF, especially after the discovery of drug resistance and paradoxical activation upon inhibitor binding to the kinase. RAF activity is regulated by phosphorylation and conformation-dependent regulation, including auto-inhibition and dimerization. In this review, we summarize the recent major findings in the study of the RAS/RAF/MEK/ERK signaling cascade, particularly with respect to the impact on clinical cancer therapy., Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
- Published
- 2020
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