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Resistance to molecularly targeted therapy in non-small-cell lung cancer

Tetsuhiko Asao1, Fumiyuki Takahashi1, Kazuhisa Takahashi1

  • 1Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.

Respiratory Investigation
|October 9, 2018
PubMed

Insights

Targeted therapies for non-small-cell lung cancer (NSCLC) show promise but often lead to drug resistance. Understanding resistance mechanisms is key to developing strategies to overcome this challenge in NSCLC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Targeted therapies based on oncogenic driver gene mutations (e.g., EGFR, ALK, ROS1, RET) have transformed non-small-cell lung cancer (NSCLC) treatment.
  • Despite initial efficacy, acquired drug resistance remains a significant clinical challenge, limiting long-term patient benefit.

Purpose of the Study:

  • To review the molecular mechanisms underlying resistance to targeted therapies in NSCLC.
  • To discuss potential strategies for overcoming acquired drug resistance in NSCLC patients.

Main Methods:

  • Literature review of studies investigating resistance mechanisms to targeted agents in NSCLC.
  • Analysis of molecular pathways implicated in the development of drug resistance.

Main Results:

  • Identified common molecular pathways and genetic alterations contributing to resistance.
  • Highlighted the heterogeneity of resistance mechanisms across different driver mutations.

Conclusions:

  • Understanding NSCLC molecular pathways is crucial for deciphering resistance mechanisms.
  • Developing novel therapeutic strategies is essential to overcome drug resistance and improve patient outcomes in NSCLC.
Keywords:
ALKAcquired resistanceEGFRLung cancerMolecularly targeted therapy

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