Mechanisms of Resistance to KRAS-Targeted Therapy

Overview

Journal Cancer Discov

Specialty Oncology

Date 2021 Apr 6

PMID 33820777

Citations 51

Authors

Neal S Akhave

Amadeo B Biter

David S Hong

Affiliations

Soon will be listed here.

Abstract

mutations are among the most common drivers of human carcinogenesis, and are associated with poor prognosis and an aggressive disease course. With the advent of KRAS inhibitors, the RAS protein is now targetable, with such inhibitors showing marked clinical responses across multiple tumor types. However, these responses are short-lived due to the development of resistance. Preclinical studies now suggest MAPK reactivation, stimulation of CDK4/6-dependent cell-cycle transition, and immune defects as possible mechanisms of resistance. Devising strategies to overcome such resistance mechanisms, which are a barrier to long-term clinical response, remain an active area of research. SIGNIFICANCE: Although KRAS-targeted cancer therapy is revolutionary, tumors rapidly develop resistance. Understanding the mechanisms driving this resistance and designing combination strategies to overcome it are integral to achieving long-term disease control.

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