Journal Article

Emerging strategies to target RAS signaling in human cancer therapy

Wang, Peng, Zhang, Yalei, Chen, Kun, Qian, Ling

2021

Overview

RAS mutations ( HRAS , NRAS , and KRAS ) are among the most common oncogenes, and around 19% of patients with cancer harbor RAS mutations. Cells harboring RAS mutations tend to undergo malignant transformation and exhibit malignant phenotypes. The mutational status of RAS correlates with the clinicopathological features of patients, such as mucinous type and poor differentiation, as well as response to anti-EGFR therapies in certain types of human cancers. Although RAS protein had been considered as a potential target for tumors with RAS mutations, it was once referred to as a undruggable target due to the consecutive failure in the discovery of RAS protein inhibitors. However, recent studies on the structure, signaling, and function of RAS have shed light on the development of RAS-targeting drugs, especially with the approval of Lumakras (sotorasib, AMG510) in treatment of KRAS G12C -mutant NSCLC patients. Therefore, here we fully review RAS mutations in human cancer and especially focus on emerging strategies that have been recently developed for RAS-targeting therapy.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Animals / Antineoplastic Agents - pharmacology / Antineoplastic Agents - therapeutic use / Cancer / Cancer Research / Cancer therapies / Care and treatment / Chemotherapy / Clinicopathological features / Colorectal cancer / Development and progression / Drug approval / Drug delivery / Drug development / Drug Discovery / Efficiency / FDA approval / Genetic aspects / Health aspects / Hematology / Hotspots / Humans / Immunotherapy / Leukemia / Lung cancer / Lung cancer, Non-small cell / Medical prognosis / Medicine / Medicine & Public Health / Melanoma / Metastasis / Molecular Targeted Therapy - methods / Mutation / Mutation - drug effects / Neoplasms - drug therapy / Neoplasms - genetics / Neoplasms - metabolism / Non-small cell lung carcinoma / Oncology / Ovarian cancer / Patients / Phenotypes / Piperazines - pharmacology / Piperazines - therapeutic use / Proteins / Pyridines - pharmacology / Pyridines - therapeutic use / Pyrimidines - pharmacology / Pyrimidines - therapeutic use / RAS mutations / Ras protein / ras Proteins - genetics / ras Proteins - metabolism / RAS-targeted therapy / Review / Signal Transduction - drug effects / Skin cancer / Structure-function relationships / Thyroid cancer / Tumors