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Therapeutical Options in ROS1-Rearranged Advanced Non Small Cell Lung Cancer

Brigida Stanzione1, Alessandro Del Conte1, Elisa Bertoli1,2

  • 1Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy.

International Journal of Molecular Sciences
|July 29, 2023
PubMed

Insights

ROS1 rearrangements in non-small cell lung cancer (NSCLC) respond to targeted therapies. Newer tyrosine kinase inhibitors (TKIs) offer improved potency and CNS activity for ROS1-positive NSCLC patients, addressing resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • ROS proto-oncogene 1 (ROS1) rearrangements are identified in 0.9-2.6% of non-small cell lung cancer (NSCLC) cases.
  • These rearrangements predict sensitivity to specific tyrosine kinase inhibitors (TKIs).

Purpose of the Study:

  • To review the clinicopathological characteristics of ROS1-positive NSCLC.
  • To summarize current and emerging therapeutic strategies for ROS1-positive NSCLC.

Main Methods:

  • Literature review of clinical trials and studies on ROS1-positive NSCLC.
  • Analysis of efficacy and resistance mechanisms of approved and investigational TKIs.

Main Results:

  • Crizotinib, a first-generation TKI, was the initial targeted therapy for ROS1-positive NSCLC.
  • Entrectinib, a potent multi-target inhibitor with enhanced CNS activity, is now approved for treatment-naive patients.
  • Resistance to TKIs can emerge after a median of 5.5-20 months, necessitating novel therapeutic approaches.

Conclusions:

  • ROS1-positive NSCLC exhibits unique clinicopathological features and therapeutic vulnerabilities.
  • The development of next-generation TKIs with increased potency and brain penetration is crucial for overcoming resistance and improving patient outcomes.
Keywords:
ROS1non small cell lung cancertarget therapy

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