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Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
MET alterations in advanced non-small cell lung cancer
Gabriel Cavalcante Lima Chagas1, Amanda Ribeiro Rangel1, Badi El Osta2
1Post-Graduation Program in Medical Sciences, Department of Internal Medicine, Faculty of Medicine, Federal University of Ceará, Costa Mendes, 1608. 4(o) andar. Rodolfo Teófilo, Fortaleza, CE 60430-140, Brazil.
Abstract:
Precision medicine has helped identify several tumor molecular aberrations to be treated with targeted therapies. These therapies showed substantial improvement in efficacy without excessive toxicity in patients with specific oncogenic drivers with advanced cancers. In metastatic lung cancers, the implementation of broad platforms for molecular tumor sequencing has helped oncology providers identify oncogenic drivers linked with better outcomes when treated upfront with targeted therapies. Mesenchymal-epithelial transition factor (MET) alterations are present in up to 60% of non-small cell lung cancer and are associated with a poor prognosis. Capmatinib and tepotinib are currently the only two approved targeted therapies by the U.S. Food and Drug Administration (FDA) for patients with MET exon 14 skipping mutation. Several agents are being developed to tackle an unmet need in patients with MET alterations. Some of these agents are being used in combination with EGFR targeted therapy to mitigate resistance to EGFR inhibitor. These agents are poised to provide new hope for these patients.
Insights
Precision medicine advances target specific cancer drivers, improving outcomes in advanced cancers. For MET-altered lung cancers, new targeted therapies offer hope against poor prognoses.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Precision medicine identifies tumor molecular aberrations for targeted therapies.
- Targeted therapies improve efficacy and reduce toxicity in advanced cancers with specific oncogenic drivers.
- Molecular tumor sequencing in metastatic lung cancers identifies drivers for improved outcomes with upfront targeted therapy.
Purpose of the Study:
- To review the role of MET alterations in non-small cell lung cancer (NSCLC).
- To discuss current and emerging targeted therapies for MET-driven NSCLC.
- To highlight the potential of combination therapies in overcoming resistance.
Main Methods:
- Literature review of precision medicine in oncology.
- Analysis of data on MET alterations in NSCLC.
- Summary of FDA-approved and investigational therapies for MET alterations.
Main Results:
- MET alterations occur in up to 60% of NSCLC and are linked to poor prognosis.
- Capmatinib and tepotinib are FDA-approved for MET exon 14 skipping mutations.
- Investigational agents are being developed, including combinations with EGFR inhibitors to combat resistance.
Conclusions:
- Targeted therapies have transformed advanced cancer treatment.
- MET alterations represent a significant challenge in NSCLC, but new agents offer promise.
- Combination strategies may overcome resistance and improve patient outcomes in MET-altered lung cancers.
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