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Updated: Aug 19, 2025

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
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Published on: December 9, 2015

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MET Signaling Pathways, Resistance Mechanisms, and Opportunities for Target Therapies

Solange Rivas1, Arnaldo Marín2, Suraj Samtani3,4

  • 1Centro de Genética y Genómica, Instituto de Ciencias e Innovación en Medicina, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago 7550000, Chile.

International Journal of Molecular Sciences
|November 26, 2022
PubMed

Insights

MET alterations drive cancer progression, but resistance to targeted therapies is a challenge. Understanding MET signaling pathways and parallel networks is key to overcoming drug resistance in lung cancer patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • The MET proto-oncogene receptor tyrosine kinase (MET) drives cancer progression via multiple signaling pathways.
  • MET driver alterations, including MET gene amplification (METamp) and MET exon 14 skipping (METex14), are crucial in lung adenocarcinoma.
  • Target therapies for MET alterations were approved in 2020, but acquired drug resistance remains a significant challenge in precision medicine.

Purpose of the Study:

  • To review the mechanisms of resistance to MET-targeted therapies.
  • To highlight the role of MET signaling pathways and parallel tyrosine kinase receptors in acquired resistance.
  • To emphasize the importance of evaluating patient mutational profiles for personalized treatment strategies.

Main Methods:

  • Literature review of studies on MET signaling, cancer progression, and drug resistance mechanisms.
  • Analysis of the interplay between MET pathways and parallel signaling networks.
  • Discussion of clinical implications for patient management and future research.

Main Results:

  • Tumor cells develop adaptive changes leading to resistance against MET inhibitors.
  • Resistance mechanisms involve not only MET signaling but also parallel tyrosine kinase receptors and shared signaling hubs.
  • Access to MET inhibitors is limited in developing countries, hindering resistance mechanism development and study.

Conclusions:

  • Understanding the complex resistance mechanisms involving MET and parallel pathways is critical for effective lung cancer treatment.
  • Pre-treatment mutational profiling and follow-up are essential to predict and mitigate drug resistance.
  • Continued collaboration between basic and clinical research is necessary to address acquired resistance to targeted therapies.
Keywords:
NSCLCactionable mutationsdriver mutationsprecision medicineresistance mutationstarget therapies

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