Affiliation:
1. State Key Laboratory of Natural Medicines, Department of Physiology, China Phar maceutical University, Nanjing 210009, China
Abstract
RAS (H-ras, K-ras, and N-ras), as the second largest mutated gene driver in various human cancers, has
long been a vital research target for cancer. Its function is to transform the extracellular environment into a cascade
of intracellular signal transduction. RAS mutant protein regulates tumor cell proliferation, apoptosis, metabolism
and angiogenesis through downstream MAPK, PI3K and other signaling pathways. In KRAS or other
RAS-driven cancers, current treatments include direct inhibitors and upstream/downstream signaling pathway
inhibitors. However, the research on these inhibitors has been largely restricted due to their escape inhibition and
off-target toxicity. In this paper, we started with the role of normal and mutant RAS genes in cancer, elucidated
the relevant RAS regulating pathways, and highlighted the important research advancements in RAS inhibitor
research. We concluded that for the crosstalk between RAS pathways, the effect of single regulation may be
limited, and the multi-target drug combined compensation mechanism is becoming a research hotspot.
Funder
China Pharmaceutical University “Double First-Class” Construction Technology Innovation Team
National Science and Technology Major Project of the Ministry of Science and Technology of China
Publisher
Bentham Science Publishers Ltd.
Subject
Drug Discovery,Pharmacology
Cited by
51 articles.
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