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RET-rearranged non-small-cell lung cancer and therapeutic implications
Zoe Loh1, Paul Mitchell1, Thomas John1,2,3
1Department of Medical Oncology, Olivia Newton-John Cancer Wellness and Research Centre, Austin Health, Melbourne, Victoria, Australia.
Abstract:
First-line tyrosine kinase inhibitors are standard of care for non-small-cell lung cancers (NSCLC) harbouring an epidermal growth factor receptor mutation, anaplastic lymphoma kinase fusion or c-ros oncogene 1 rearrangement. Other targetable oncogenic drivers have been identified but testing for these is neither funded nor commonly performed in Australia. Using a case example, we discuss the importance of considering several other genomic aberrations in our population, such as rearrangements in the RET proto-oncogene, which occur in 1-2% of lung adenocarcinoma. New oncogenic drivers and corresponding targeted agents are constantly being discovered; these will continue to refine the treatment of non-small-cell lung cancer in the era of precision medicine.
Insights
Testing for rare oncogenic drivers in non-small-cell lung cancer (NSCLC) is crucial for effective precision medicine. Identifying targets like RET proto-oncogene rearrangements improves treatment outcomes for lung adenocarcinoma patients.
Area of Science:
- Oncology
- Genomics
- Precision Medicine
Background:
- Standard first-line treatments for non-small-cell lung cancer (NSCLC) target specific mutations like EGFR, ALK, and ROS1.
- Comprehensive genomic profiling for other targetable oncogenic drivers is not standard practice or funded in Australia.
Observation:
- A case example highlights the significance of considering less common genomic alterations in NSCLC.
- RET proto-oncogene rearrangements, found in 1-2% of lung adenocarcinoma, represent a targetable driver.
Findings:
- Current NSCLC diagnostic protocols in Australia do not routinely include testing for all identified oncogenic drivers.
- The identification of novel drivers and targeted therapies is continuously advancing NSCLC treatment.
Implications:
- Expanding genomic testing beyond common mutations can improve treatment selection for a broader NSCLC patient population.
- Integrating comprehensive profiling into clinical practice is essential for advancing precision oncology in lung cancer.
- Future NSCLC management will increasingly rely on identifying rare drivers and utilizing novel targeted agents.
