Nanosized Modification Strategies for Improving the Antitumor Efficacy of MEK Inhibitors

Author(s): Yanan Li, Qingrong Dong, Ting Mei, Meichen Zheng, Ramasamy Raj Kumar, Bin Yu, Chunsheng Wu, Hui Zhang*, Feifei An*.

Journal Name: Current Drug Targets

Volume 21 , Issue 3 , 2020

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Graphical Abstract:


Abstract:

The RAS-RAF-MEK-ERK signaling pathway (MAPK signaling) is hyperactivated in more than 30% of human cancers. The abnormal activation of this pathway is mainly due to the gain-offunction mutations in RAS or RAF genes. Furthermore, the crucial roles of mitogen-activated protein kinase kinase (MEK) in tumorigenesis, cell proliferation and apoptosis inhibition, make MEK inhibitors (MEKi) attractive candidates for the targeted therapy of MAPK pathway-related cancer. Several highly selective and potent non-ATP-competitive allosteric MEKi have been developed and have led to substantial improvements in clinical outcomes. However, the drug efficacies and response rates are limited due to complex pathway cross-talk and pessimistic drug solubility. Nanosized modifications have made great contributions to improving drug efficacies over the past decades. In this review, the important biological status of MEK kinase in the MAPK pathway is illuminated primarily to highlight the irreplaceable position and clinical status of MEKi. In addition, nanomodification strategies to enhance drug efficacy are briefly summarized, followed by the application advances of nanotechnology in the field of MEKi-related cancer theranostics. Finally, the obstacles impeding the development of nanosized MEKi are considered, and promising prospects are suggested. This informative report lays the groundwork for the clinical development of MEKi and outlines a rational frontline-treatment approach for personalized cancer treatment.

Keywords: Nanomedicine, modification strategy, MAPK signaling pathway, MEK inhibitor, enhanced drug efficacy, targeted cancer theranostics.

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VOLUME: 21
ISSUE: 3
Year: 2020
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DOI: 10.2174/1389450120666190807143245
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