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Beyond ALK-RET, ROS1 and other oncogene fusions in lung cancer

Takashi Kohno1, Takashi Nakaoku1, Koji Tsuta1

  • 11 Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan ; 2 Division of Translational Research, Exploratory Oncology Research & Clinical Trial Center (EPOC), National Cancer Center, Tokyo and Chiba, Japan ; 3 Division of Thoracic Oncology, National Cancer Center Hospital East, Chiba, Japan ; 4 Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan.

Translational Lung Cancer Research
|April 15, 2015
PubMed

Insights

New genetic targets, RET and ROS1 fusions, offer promising treatment strategies for non-small cell lung cancer (NSCLC). Inhibiting these fusions with tyrosine kinase inhibitors (TKIs) is a key focus in ongoing clinical trials for specific patient groups.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Non-small cell lung cancer (NSCLC) harbors various genetic aberrations.
  • RET and ROS1 oncogene fusions represent newly identified targetable aberrations in NSCLC.
  • These fusions are often found in specific patient demographics, including young, female, and never-smokers.

Purpose of the Study:

  • To highlight RET and ROS1 fusions as significant genetic aberrations in NSCLC.
  • To emphasize the therapeutic potential of inhibiting RET and ROS1 kinase activity.
  • To discuss the role of multiplex diagnostic systems in advancing personalized lung cancer therapy.

Main Methods:

  • Review of in vitro and in vivo models studying RET and ROS1 fusion proteins.
  • Analysis of clinical data from patients with fusion-positive lung cancer.
  • Identification of other targetable gene fusions (NTRK1, NRG1, FGFR1/2/3) in NSCLC.

Main Results:

  • RET and ROS1 fusions are actionable targets in NSCLC lacking other common oncogenic drivers.
  • Inhibition of RET and ROS1 fusion proteins shows therapeutic promise.
  • Ongoing clinical trials are evaluating tyrosine kinase inhibitors (TKIs) for these fusions.
  • Other targetable fusions like NTRK1, NRG1, and FGFR are also present in NSCLC.

Conclusions:

  • Targeting RET and ROS1 fusions represents a promising therapeutic avenue for NSCLC.
  • Tyrosine kinase inhibitors (TKIs) are effective against RET and ROS1 fusion proteins.
  • Multiplex diagnostic systems can enhance personalized therapy options by detecting multiple druggable gene fusions in NSCLC.
Keywords:
RET fusionROS1 fusionmultiplex diagnosis systemoncogene fusiontyrosine kinase inhibitor (TKI)

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