Activated RET and ROS: two new driver mutations in lung adenocarcinoma

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Rearrangements of ROS1 and RET are recently identified driver mutations in lung adenocarcinoma.
• These genetic alterations define unique molecular subsets with minimal overlap with other known lung adenocarcinoma drivers.
• ROS1 and RET rearrangements occur in approximately 1% of lung adenocarcinoma cases each.

Purpose of the Study:

• To review the clinicopathologic characteristics of lung adenocarcinoma with RET and ROS1 rearrangements.
• To discuss the in vitro and clinical activity of targeted therapies against these genetic alterations.
• To highlight the potential for personalized treatment strategies in lung cancer.

Main Methods:

• Review of existing literature on ROS1 and RET rearrangements in lung adenocarcinoma.
• Analysis of clinical trial data for kinase inhibitors targeting these alterations.
• Evaluation of in vitro studies assessing drug activity in relevant cancer cells.

Main Results:

• Specific clinicopathologic features are associated with RET and ROS1 rearrangements.
• Several multi-targeted receptor kinase inhibitors demonstrate in vitro efficacy against NSCLC cells with these alterations.
• Crizotinib exhibits significant clinical activity in patients with advanced ROS1-positive lung cancer.

Conclusions:

• Ongoing clinical trials are evaluating various kinase inhibitors for RET and ROS1 rearranged lung adenocarcinoma.
• Personalized treatment approaches for these genetically defined lung cancer subsets are likely to be implemented soon.
• Targeted therapies represent a promising future direction for managing specific lung adenocarcinoma patient populations.