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Secondary Resistant Mutations to Small Molecule Inhibitors in Cancer Cells

Abdulaziz B Hamid1, Ruben C Petreaca1

  • 1Department of Molecular Genetics, The Ohio State University, Marion, OH 43302, USA.

Cancers
|April 15, 2020
PubMed

Insights

Cancer cells develop resistance to small molecule inhibitors through various mutations, leading to recurrence and more aggressive disease. This review comprehensively analyzes these resistant mutations and their underlying mechanisms.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Small molecule inhibitors are crucial in cancer therapy.
  • Secondary resistant mutations frequently emerge, causing treatment failure.
  • These mutations lead to cancer recurrence and progression.

Purpose of the Study:

  • To provide a comprehensive review of resistant mutations in cancer.
  • To discuss the mechanistic parallels of resistance to small molecule inhibitors.
  • To build upon existing compendia of cancer mutations.

Main Methods:

  • Literature review of resistant mutations in cancer.
  • Analysis of data from the Catalogue of Somatic Mutations in Cancer (COSMIC).
  • Discussion of resistance mechanisms, including altered drug affinity, enzyme function restoration, and pathway activation.

Main Results:

  • Resistant mutations can decrease drug-target affinity.
  • Mutations can restore enzyme function despite inhibitor presence.
  • Activation of parallel pathways is a common resistance mechanism.

Conclusions:

  • Understanding resistant mutations is key to overcoming treatment failure.
  • Mechanistic insights can guide the development of new therapeutic strategies.
  • Comprehensive reviews are vital for tracking and combating cancer resistance.
Keywords:
cellular adaptationcombination therapyresistant mutationsmall molecule inhibitortargeted therapy

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