Oncotarget
A Rare Genetic Shift That Helped Lung Cancer Evade Treatment
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Quick takeaways
- The identification of the RUFY1-RET rearrangement reveals a significant mechanism by which lung cancer can develop resistance to targeted therapies like lorlatinib.
- The case underscores the critical need for advanced genetic testing in personalized cancer treatment, as standard methods may overlook crucial mutations.
Deep dives
Mechanism of Resistance in Lung Cancer Treatment
A rare genetic alteration called the RU-F1 rearrangement was identified as a mechanism allowing lung cancer to develop resistance to lorlatinib, a targeted therapy for non-small cell lung cancer (NSCLC). This case involved a 42-year-old patient with advanced NSCLC, initially responding well to treatments like intrectinib and lorlatinib before his cancer began to progress. Through RNA next-generation sequencing, clinicians discovered a previously unknown RUFY1-RET fusion mutation, marking the first documented instance of a RET fusion contributing to resistance against ROS1 inhibitors. This finding emphasizes the necessity of advanced genetic testing for personalized cancer treatment, as standard DNA testing failed to detect this critical mutation.
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