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Updated: Mar 26, 2026

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
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Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Published on: December 9, 2015

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ALK and ROS1 as targeted therapy paradigms and clinical implications to overcome crizotinib resistance

Mingxiang Ye1, Xinxin Zhang1, Nan Li1

  • 1Department of Pulmonary Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Oncotarget
|January 24, 2016
PubMed

Insights

Targeted therapies like crizotinib show promise for non-small cell lung cancer (NSCLC) patients with ALK or ROS1 rearrangements. Overcoming acquired resistance to these treatments is crucial for long-term patient benefit.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Non-small cell lung cancer (NSCLC) has over 10 validated targetable oncogenic driver genes.
  • Anaplastic lymphoma kinase (ALK) and ROS1 rearrangements define a subset of NSCLC.
  • Crizotinib effectively targets ALK- and ROS1-rearranged NSCLC but acquired resistance is a challenge.

Purpose of the Study:

  • To review the biology of ALK and ROS1 in cancer progression.
  • To summarize clinical trials targeting ALK and ROS1.
  • To discuss mechanisms of crizotinib resistance and strategies to overcome it.

Main Methods:

  • Literature review of ALK and ROS1 biology.
  • Summary of clinical trial data for ALK/ROS1 inhibitors.
  • Analysis of molecular mechanisms underlying crizotinib resistance.

Main Results:

  • ALK and ROS1 rearrangements are key drivers in a subset of NSCLC.
  • Crizotinib demonstrates high efficacy but is associated with eventual resistance.
  • Understanding resistance mechanisms is vital for developing next-generation therapies.

Conclusions:

  • Targeting ALK and ROS1 offers a promising therapeutic strategy for NSCLC.
  • Further research into overcoming crizotinib resistance is essential.
  • This review provides insights into novel targeted cancer therapies.
Keywords:
ROS1 kinaseanaplastic lymphoma kinasecrizotinibdrug resistancenon-small cell lung cancer

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