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Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
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Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing

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Therapeutic approaches for T790M mutation positive non-small-cell lung cancer

Ilaria Attili1, Niki Karachaliou2,3, PierFranco Conte1

  • 1a Department of Surgical, Oncological and Gastroenterological Sciences , University of Padova , Padova , Italy.

Expert Review of Anticancer Therapy
|August 7, 2018
PubMed
Abstract

Insights

T790M mutations cause resistance to targeted lung cancer therapies. Osimertinib is a key treatment for EGFR mutation-positive non-small cell lung cancer (NSCLC) with this resistance, though new strategies are emerging.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) shows initial response to targeted therapies.
  • Acquired resistance, often due to the T790M mutation in 50-60% of cases, limits long-term efficacy of first-generation EGFR tyrosine kinase inhibitors (TKIs).
  • Understanding T790M mutation is crucial for managing advanced NSCLC.

Purpose of the Study:

  • To review the significance of the T790M resistance mutation in EGFR-mutated NSCLC.
  • To discuss current methods for T790M mutation detection.
  • To outline treatment strategies and emerging resistance mechanisms.

Main Methods:

  • Literature review of studies on T790M mutation in NSCLC.
  • Analysis of clinical trial data for T790M-targeted therapies.
  • Overview of diagnostic techniques for T790M detection.

Main Results:

  • Osimertinib is the current standard of care for T790M-positive NSCLC post-progression on first/second-generation EGFR TKIs.
  • Osimertinib demonstrates efficacy, including in cases with brain metastases.
  • Emerging resistance mechanisms to Osimertinib are under investigation.

Conclusions:

  • The T790M mutation is a critical determinant of resistance in EGFR-mutated NSCLC.
  • Osimertinib offers a valuable therapeutic option for patients with T790M-positive NSCLC.
  • Ongoing research is exploring first-line applications and combination strategies for improved outcomes.
Keywords:
EGFRTKI resistanceliquid biopsylung cancerosimertinib

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