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Updated: Oct 20, 2025
Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
Lung cancer treated abroad with receptor tyrosine kinase inhibitor
Background:
Activating RET fusions are oncogenic drivers in multiple cancers and are identified in 1-2 % of non-small cell lung cancers (NSCLC). Selpercatinib and pralsetinib are tyrosine kinase inhibitors selectively targeting RET and with clinical activity in RET-positive NSCLC.
Case Presentation:
A male never-smoker in his forties was diagnosed with advanced lung adenocarcinoma. With negative tests for EGFR mutations, ROS1 and ALK rearrangements, he was treated with a combination of chemotherapy and an immune checkpoint inhibitor. Upon progression a rebiopsy analysed by next generation sequencing (NGS) revealed a KIF5B-RET fusion. He received treatment with pralsetinib through a compassionate use programme, with relief of symptoms within weeks, and radiological partial response after two months of treatment. He has not experienced side effects after six months of treatment.
Interpretation:
Precision medicine is dependent on diagnostic methods such as NGS to identify patients who might benefit from targeted therapies. Selective inhibitors of molecular oncogenic drivers are usually effective and well tolerated.
Insights
Activating RET fusions drive cancer, including non-small cell lung cancer (NSCLC). Targeted therapy with pralsetinib showed significant clinical activity and tolerability in a patient with a KIF5B-RET fusion.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Activating RET fusions are oncogenic drivers in various cancers, including 1-2% of non-small cell lung cancers (NSCLC).
- Selpercatinib and pralsetinib are selective tyrosine kinase inhibitors targeting RET, demonstrating clinical activity in RET-positive NSCLC.
Observation:
- A never-smoker male patient in his forties presented with advanced lung adenocarcinoma.
- Initial treatments with chemotherapy and immunotherapy were ineffective.
- Next-generation sequencing (NGS) identified a KIF5B-RET fusion after disease progression.
Findings:
- The patient received pralsetinib via a compassionate use program.
- Symptomatic relief was observed within weeks of treatment initiation.
- Radiological partial response was achieved after two months, with no reported side effects after six months.
Implications:
- Precision medicine relies on diagnostic tools like NGS to identify patients for targeted therapies.
- Selective inhibitors targeting molecular oncogenic drivers offer effective and well-tolerated treatment options.
- This case highlights the potential of RET-targeted therapies in specific NSCLC patient populations.
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