Targeting rare and non-canonical driver variants in NSCLC – An uncharted clinical field
| Autor: | Eugen Rempel, Peter Horak, Roland Penzel, Anna-Lena Volckmar, Claus Peter Heußel, Michael Allgäuer, Michael Thomas, Regine Brandt, Huriye Seker-Cin, Mark Kriegsmann, Volker Endris, Jan Budczies, Olaf Neumann, Jonas Leichsenring, Tilman Brummer, Felix J.F. Herth, Petros Christopoulos, M. Faehling, Jürgen Fischer, Daniel Kazdal, Albrecht Stenzinger, Martina Kirchner, Julia Glade, Tilmann Bochtler, Hauke Winter, Peter Schirmacher, Stefan Fröhling, Hannah Goldschmid |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Oncology Cancer Research medicine.medical_specialty Lung Neoplasms 03 medical and health sciences 0302 clinical medicine Carcinoma Non-Small-Cell Lung Proto-Oncogene Proteins Thoracic Oncology Internal medicine ROS1 medicine Humans Precision Medicine Lung cancer business.industry High-Throughput Nucleotide Sequencing Protein-Tyrosine Kinases medicine.disease Clinical trial 030104 developmental biology Non canonical Precision oncology 030220 oncology & carcinogenesis Mutation Molecular targets business Systematic search |
| Zdroj: | Lung Cancer. 154:131-141 |
| ISSN: | 0169-5002 |
| Popis: | Objectives Implementation of tyrosine kinase inhibitors (TKI) and other targeted therapies was a main advance in thoracic oncology with survival gains ranging from several months to years for non-small-cell lung cancer (NSCLC) patients. High-throughput comprehensive molecular profiling is of key importance to identify patients that can potentially benefit from these novel treatments. Material and Methods Next-generation sequencing (NGS) was performed on 4500 consecutive formalin-fixed, paraffin-embedded specimens of advanced NSCLC (n = 4172 patients) after automated extraction of DNA and RNA for parallel detection of mutations and gene fusions, respectively. Results and Conclusion Besides the 24.9 % (n = 1040) of cases eligible for approved targeted therapies based on the presence of canonical alterations in EGFR exons 18–21, BRAF, ROS1, ALK, NTRK, and RET, an additional n = 1260 patients (30.2 %) displayed rare or non-canonical mutations in EGFR (n = 748), BRAF (n = 135), ERBB2 (n = 30), KIT (n = 32), PIK3CA (n = 221), and CTNNB1 (n = 94), for which targeted therapies could also be potentially effective. A systematic literature search in conjunction with in silico evaluation identified n = 232 (5.5 %) patients, for which a trial of targeted treatment would be warranted according to available evidence (NCT level 1, i.e. published data showing efficacy in the same tumor entity). In conclusion, a sizeable fraction of NSCLC patients harbors rare or non-canonical alterations that may be associated with clinical benefit from currently available targeted drugs. Systematic identification and individualized management of these cases can expand applicability of precision oncology in NSCLC and extend clinical gain from established molecular targets. These results can also inform clinical trials. |
| Databáze: | OpenAIRE |
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