The Landscape of Actionable Gene Fusions in Colorectal Cancer
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Updated: Jan 3, 2026
Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing
Published on: July 5, 2019
Filippo Pagani1, Giovanni Randon1, Vincenzo Guarini1
1Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milano, Italy.
Abstract:
The treatment scenario of metastatic colorectal cancer (mCRC) has been rapidly enriched with new chemotherapy combinations and biological agents that lead to a remarkable improvement in patients' outcome. Kinase gene fusions account for less than 1% of mCRC overall but are enriched in patients with high microsatellite instability, RAS/BRAF wild-type colorectal cancer. mCRC patients harboring such alterations show a poor prognosis with standard treatments that could be reversed by adopting novel therapeutic strategies. Moving forward to a positive selection of mCRC patients suitable for targeted therapy in the era of personalized medicine, actionable gene fusions, although rare, represent a peculiar opportunity to disrupt a tumor alteration to achieve therapeutic goal. Here we summarize the current knowledge on potentially actionable gene fusions in colorectal cancer available from retrospective experiences and promising preliminary results of new basket trials.
Insights
Actionable kinase gene fusions, though rare in metastatic colorectal cancer (mCRC), offer targeted therapy opportunities. Identifying these fusions can improve outcomes for patients with high microsatellite instability and wild-type RAS/BRAF status.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Metastatic colorectal cancer (mCRC) treatment has advanced with new therapies.
- Kinase gene fusions are rare (<1%) in mCRC but prevalent in microsatellite instability-high, RAS/BRAF wild-type tumors.
- Standard treatments yield poor prognoses for mCRC patients with these alterations.
Purpose of the Study:
- To summarize current knowledge on actionable gene fusions in colorectal cancer.
- To highlight the potential of targeted therapies for specific mCRC patient subgroups.
- To review findings from retrospective studies and early-phase basket trials.
Main Methods:
- Literature review of retrospective experiences.
- Analysis of preliminary results from new basket trials.
- Focus on actionable kinase gene fusions in colorectal cancer.
Main Results:
- Kinase gene fusions are enriched in a specific subset of mCRC patients.
- These alterations are associated with poor prognosis under standard care.
- Novel therapeutic strategies targeting gene fusions show promise.
Conclusions:
- Actionable gene fusions represent a unique target for therapeutic intervention in mCRC.
- Personalized medicine approaches can leverage these rare alterations for improved patient outcomes.
- Further research in basket trials is crucial for validating targeted strategies.
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