MEK inhibitors in oncology: a patent review (2015-Present)

Expert Opin Ther Pat. 2017 Aug;27(8):887-906. doi: 10.1080/13543776.2017.1339688. Epub 2017 Jun 19.

Abstract

The RAS/RAF/MEK/ERK and PI3K/AKT/mTOR signaling pathways have been identified as promising therapeutic targets for cancer therapy. Over-activation of these pathways and their components including gene mutations has been considered as one of the major causes of melanoma. Mitogen-activated protein kinase (MEK) is a downstream kinase of RAS pathway found in two different forms MEK1/2. The MEK inhibitors in combination with other kinase/mutant gene inhibitors have shown promising results in patients with metastatic melanoma. Areas covered: A comprehensive review of the patent literature (2015 - Present) on MEK inhibitors, their combinations with other kinase inhibitors and structural insights has been highlighted. Expert opinion: Recently mitogen-activated protein kinase (MEK) inhibitors have attracted considerable interest in oncology especially in melanoma. The MEK inhibitors showed promising results in patients with metastatic melanoma harboring mutant genes such as BRAF, KRAS. The MEK1/2 inhibitors in combination with BRAF, KRAS and/or PI3K inhibitors showed promising results in mutated colorectal, pancreatic adenocarcinoma, solid tumor, and relapsed/refractory melanoma. The combination delays the onset of acquired resistance, resulting in increased progression-free and overall survival. The combination and/or multi-targeted kinase/mutant gene inhibitors may be a therapeutic option for the personalized cancer treatment of patients with relapsed or refractory multiple myeloma.

Keywords: Cancer; MEK; clinical trials; inhibitors; melanoma; mutation; patent; personalized medicine.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology
  • Disease-Free Survival
  • Drug Design
  • Humans
  • Melanoma / drug therapy
  • Melanoma / enzymology
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Molecular Targeted Therapy
  • Multiple Myeloma / drug therapy
  • Multiple Myeloma / enzymology
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Neoplasms / pathology
  • Patents as Topic
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / pharmacology*
  • Survival Rate

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Mitogen-Activated Protein Kinase Kinases