Fusions in solid tumours: Diagnostic strategies, targeted therapy, and acquired resistance Journal Article
| Authors: | Schram, A. M.; Chang, M. T.; Jonsson, P.; Drilon, A. |
| Article Title: | Fusions in solid tumours: Diagnostic strategies, targeted therapy, and acquired resistance |
| Abstract: | Structural gene rearrangements resulting in gene fusions are frequent events in solid tumours. The identification of certain activating fusions can aid in the diagnosis and effective treatment of patients with tumours harbouring these alterations. Advances in the techniques used to identify fusions have enabled physicians to detect these alterations in the clinic. Targeted therapies directed at constitutively activated oncogenic tyrosine kinases have proven remarkably effective against cancers with fusions involving ALK, ROS1, or PDGFB, and the efficacy of this approach continues to be explored in malignancies with RET, NTRK1/2/3, FGFR1/2/3, and BRAF/CRAF fusions. Nevertheless, prolonged treatment with such tyrosine-kinase inhibitors (TKIs) leads to the development of acquired resistance to therapy. This resistance can be mediated by mutations that alter drug binding, or by the activation of bypass pathways. Second-generation and third-generation TKIs have been developed to overcome resistance, and have variable levels of activity against tumours harbouring individual mutations that confer resistance to first-generation TKIs. The rational sequential administration of different inhibitors is emerging as a new treatment paradigm for patients with tumours that retain continued dependency on the downstream kinase of interest. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. |
| Keywords: | signal transduction; treatment outcome; genetics; mutation; review; sorafenib; erlotinib; sunitinib; nonhuman; antineoplastic agents; drug targeting; pathophysiology; antineoplastic agent; cancer diagnosis; neoplasm; neoplasms; phenotype; animal; metabolism; animals; gene; gene targeting; imatinib; diagnostic procedure; genetic predisposition to disease; gene expression profiling; molecular dynamics; cytogenetics; enzyme activation; drug resistance; pathology; drug resistance, neoplasm; dasatinib; fibroblast growth factor receptor 3; tumor marker; carcinogenesis; protein tyrosine kinase inhibitor; oncogene; diagnostic value; gefitinib; gene fusion; pazopanib; vandetanib; predictive value of tests; therapy effect; tumor growth; nilotinib; genetic predisposition; b raf kinase; lapatinib; fibroblast growth factor receptor 1; fibroblast growth factor receptor 2; predictive value; personalized medicine; braf gene; brain derived neurotrophic factor receptor; molecularly targeted therapy; molecular diagnosis; molecular diagnostic techniques; genetic transformation; molecular targeted therapy; crizotinib; vemurafenib; genetic resistance; ret gene; next generation sequencing; cancer prognosis; drug effects; dabrafenib; cabozantinib; alk gene; fgfr1 gene; ponatinib; regorafenib; fgfr3 gene; ros1 gene; humans; human; priority journal; precision medicine; ceritinib; prognostic assessment; alectinib; brigatinib; entrectinib; biomarkers, tumor; lorlatinib; ntrk3 gene; solid malignant neoplasm; apatinib; larotrectinib; craf gene; fgfr2 gene; ntrk1 gene; ntrk2 gene; pdgfb gene |
| Journal Title: | Nature Reviews Clinical Oncology |
| Volume: | 14 |
| Issue: | 12 |
| ISSN: | 1759-4774 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2017-12-01 |
| Start Page: | 735 |
| End Page: | 748 |
| Language: | English |
| DOI: | 10.1038/nrclinonc.2017.127 |
| PUBMED: | 28857077 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Review -- Export Date: 2 January 2018 -- Source: Scopus |
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