Title:The Therapeutic Potential of MEK1/2 Inhibitors in the Treatment of Gynecological Cancers: Rational Strategies and Recent Progress
Volume: 20
Issue: 6
Author(s): Sadaf Ghanaatgar-Kasbi, Majid Khazaei, Azam Rastgar-Moghadam, Gordon A. Ferns, Seyed Mahdi Hassanian and Amir Avan*
Affiliation:
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad,Iran
Keywords:
Mitogen-activated protein kinase pathway, MEK1/2 inhibitors, gynecologic cancers, tumorigenesis, anticancer
activity, WX-554.
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.
