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Updated: Oct 7, 2025

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
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Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Published on: December 9, 2015

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Experimental Determination of Cancer Drug Targets with Independent Mechanisms of Resistance

Abigail R Bland1, Nensi Shrestha1, Maddie Berry1

  • 1Department of Pharmacology & Toxicology, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand.

Current Cancer Drug Targets
|January 7, 2022
PubMed

Insights

Mathematical modeling suggests combining cancer drugs with different resistance mechanisms is effective. Experiments using lung cancer cells identified criteria for ideal drug combinations, with ALK and MEK inhibitors showing the most promise.

Area of Science:

  • Oncology
  • Cancer Biology
  • Pharmacology

Background:

  • Mathematical modeling indicates that combining cancer drugs with distinct resistance mechanisms can delay drug resistance.
  • Identifying suitable drug combinations that target different resistance pathways remains a challenge in cancer therapy.

Purpose of the Study:

  • To establish experimental criteria for selecting effective drug combinations to overcome or delay cancer drug resistance.
  • To evaluate different drug combinations in anaplastic lymphoma kinase (ALK) mutated lung cancer cells based on these criteria.

Main Methods:

  • Development of four experimental criteria to assess the suitability of drug combinations for combination therapy.
  • Application of these criteria to experimental models of anaplastic lymphoma kinase (ALK) mutated lung cancer.
  • Testing of various drug combinations, including ALK and MEK inhibitors.

Main Results:

  • Experimental data guided by the proposed criteria were generated for anaplastic lymphoma kinase (ALK) mutated lung cancer.
  • Different drug combinations were evaluated, demonstrating varying degrees of success in meeting the established criteria.
  • The combination of anaplastic lymphoma kinase (ALK) and MEK inhibitors demonstrated the strongest alignment with all proposed criteria.

Conclusions:

  • The study proposes essential experimental criteria for the rational design of combination cancer therapies.
  • The combination of anaplastic lymphoma kinase (ALK) and MEK inhibitors shows significant potential for overcoming or delaying drug resistance in ALK-mutated lung cancer.
  • Further research is warranted to validate these findings and explore the clinical applicability of the proposed drug combinations.
Keywords:
ALKcombination treatmentdrug resistancedrug targetslung cancermathematical modelling

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