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ROS1-rearranged Non-small Cell Lung Cancer

Nicholas P Giustini1, Lyudmila Bazhenova2

  • 1UCSD Moores Cancer Center, 3855 Health Sciences Drive #0829, La Jolla, CA 92093-0829, USA.

Thoracic Surgery Clinics
|April 25, 2020
PubMed

Insights

ROS1-rearranged non-small cell lung cancer (NSCLC) is driven by ROS1 kinase and initially responds to tyrosine kinase inhibitors (TKIs). Acquired resistance to TKIs can occur through secondary mutations or bypass pathways, necessitating further investigation of novel TKI therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • ROS1-rearranged non-small cell lung cancer (NSCLC) accounts for 1-2% of all NSCLC cases.
  • This cancer subtype is characterized by a constitutively activated ROS1 kinase due to gene rearrangements.
  • Current diagnostic methods can detect these ROS1 alterations.

Purpose of the Study:

  • To summarize the oncogenic drivers and initial treatment strategies for ROS1-rearranged NSCLC.
  • To describe the mechanisms of acquired resistance to tyrosine kinase inhibitors (TKIs) in this patient population.
  • To highlight ongoing investigations into novel TKI therapies for resistant ROS1-rearranged NSCLC.

Main Methods:

  • Literature review of studies on ROS1-rearranged NSCLC.
  • Analysis of clinical trial data for TKI efficacy and resistance patterns.
  • Review of molecular mechanisms underlying TKI resistance.

Main Results:

  • ROS1-rearranged NSCLC is initially sensitive to TKIs targeting the activated ROS1 kinase.
  • Acquired resistance to TKIs develops via secondary kinase mutations or activation of bypass signaling pathways.
  • These resistance mechanisms subvert the oncogenic dependence on ROS1.

Conclusions:

  • Understanding resistance mechanisms is crucial for developing effective long-term treatment strategies for ROS1-rearranged NSCLC.
  • Further investigation of TKIs demonstrating efficacy in patients with secondary resistance is warranted.
  • The development of next-generation TKIs is essential for overcoming treatment resistance in ROS1-rearranged NSCLC.
Keywords:
Lung cancerNon–small cell lung cancer (NSCLC)ROS1 fusionROS1 inhibitorROS1 rearrangementResistance mechanismTargeted therapyTyrosine kinase inhibitor (TKI)

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