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Current Cancer Drug Targets

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Review Article

The Therapeutic Potential of MEK1/2 Inhibitors in the Treatment of Gynecological Cancers: Rational Strategies and Recent Progress

Author(s): Sadaf Ghanaatgar-Kasbi, Majid Khazaei, Azam Rastgar-Moghadam, Gordon A. Ferns, Seyed Mahdi Hassanian and Amir Avan*

Volume 20 , Issue 6 , 2020

Page: [417 - 428] Pages: 12

DOI: 10.2174/1568009620666200424144303

Price: $65

Abstract

The mitogen-activated protein kinase (MAPK) pathway is among the key factors in numerous cellular processes involved in tumorigenesis, suggesting it as a potential therapeutic target in gynecological cancer. MAPKs connect gene expression pathways and external stimulations. They include a network consisting of Ras, Raf or MAP3K, MEK or MAP2K, ERK or MAPK. Among these, MEK is an attractive molecular target of novel cancer therapeutics as it joints upstream activators and their corresponding downstream targets. MEK inhibitors were among the first inhibitors of the MAPK pathway entering into clinical trials. Several drugs have recently been developed as MEK inhibitors. MEK1/2 inhibitors demonstrate promising efficacy and anticancer activity to treat this malignancy and captured much attention in the past decade. Here, we summarize the role of MAPK/MEK/ERK pathway in the pathogenesis of gynecological cancer, with particular emphasis on MEK inhibitors in clinical settings, including PD-0325901, Selumetinib, Cobimetinib, Refametinib, Trametinib, Pimasertib, MEK162 and WX-554 in gynecologic cancers.

Keywords: Mitogen-activated protein kinase pathway, MEK1/2 inhibitors, gynecologic cancers, tumorigenesis, anticancer activity, WX-554.

Graphical Abstract

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