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Updated: Feb 23, 2026

Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing
Published on: July 5, 2019
Fusions in solid tumours: diagnostic strategies, targeted therapy, and acquired resistance
Alison M Schram1, Matthew T Chang2, Philip Jonsson2
1Department of Medicine 1275 York Avenue, New York, New York 10065, USA.
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.
Insights
Gene fusions in solid tumors drive cancer. Targeted therapies like tyrosine-kinase inhibitors (TKIs) are effective but lead to resistance, prompting development of new TKIs and sequential treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Structural gene rearrangements leading to gene fusions are common in solid tumors.
- Identifying activating gene fusions aids in tumor diagnosis and targeted treatment.
- Targeted therapies against oncogenic tyrosine kinases have shown success in specific cancers.
Purpose of the Study:
- To review the role of gene fusions in solid tumors.
- To discuss the efficacy and limitations of tyrosine-kinase inhibitors (TKIs).
- To explore emerging treatment strategies for overcoming TKI resistance.
Main Methods:
- Literature review of studies on gene fusions and targeted therapies in solid tumors.
- Analysis of mechanisms of acquired resistance to TKIs.
- Evaluation of second- and third-generation TKIs and sequential treatment approaches.
Main Results:
- Activating gene fusions are crucial biomarkers for targeted therapy in various solid tumors.
- Tyrosine-kinase inhibitors (TKIs) targeting ALK, ROS1, PDGFB, RET, NTRK, FGFR, and BRAF/CRAF fusions demonstrate clinical efficacy.
- Acquired resistance to TKIs, driven by mutations or bypass pathways, necessitates the development of next-generation inhibitors and strategic treatment sequencing.
Conclusions:
- Gene fusions represent important therapeutic targets in oncology.
- Overcoming acquired resistance to TKIs is critical for long-term patient benefit.
- Sequential administration of different TKIs is a promising strategy for managing TKI-resistant tumors.
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