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Updated: Nov 12, 2025

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Uncommon targets in non-small cell lung cancer: Everyone wants a slice of cake

Alessandro De Toma1, Giuseppe Lo Russo1, Diego Signorelli1

  • 1Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Critical Reviews in Oncology/Hematology
|March 16, 2021
PubMed

Insights

Targeted therapies offer improved outcomes for non-small cell lung cancer (NSCLC) patients with EGFR and ALK alterations. This review explores emerging therapies for uncommon NSCLC alterations like ROS1, BRAF, and MET.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Targeted therapies have revolutionized non-small cell lung cancer (NSCLC) treatment for EGFR-mutated and ALK-rearranged patients.
  • These therapies offer superior outcomes and a better toxicity profile than traditional chemotherapy.

Purpose of the Study:

  • To review uncommon molecular alterations in NSCLC beyond EGFR and ALK.
  • To discuss emerging and investigational therapies targeting these alterations.
  • To summarize patient characteristics, therapeutic strategies, and resistance mechanisms.

Main Methods:

  • Literature review of recent clinical trials and research publications.
  • Analysis of data on novel drug targets and treatment approaches for NSCLC.
  • Synthesis of information on rare genetic alterations and their clinical implications.

Main Results:

  • Focus on uncommon alterations including ROS1, BRAF, RET, HER2, NTRK, and MET.
  • Identification of approved and investigational drugs for these targets.
  • Discussion of resistance mechanisms to targeted therapies.

Conclusions:

  • Emerging targeted therapies show promise for NSCLC patients with uncommon alterations.
  • Further research is needed to optimize treatment strategies and overcome resistance.
  • Personalized medicine approaches are expanding in NSCLC treatment.
Keywords:
Non-small cell lung cancerResistance mechanismTarget therapyUncommon alterations

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