Hepatology (Baltimore, Md.)
September 22, 2025 · via Europe PMC
Evolving precision: Updates in targeted therapy for cholangiocarcinoma.
Tesini G, Ibrahim H, Rimassa L, Braconi C.
AI summary — for doctors, generated from the abstract only
This review describes how next-generation sequencing-identified actionable mutations, found in roughly half of biliary tract cancer (BTC) patients, have led to targeted therapies now recommended for fit patients after first-line chemotherapy, despite lacking head-to-head trials against standard second-line chemotherapy.
What was studied
A narrative review of precision/targeted therapy for biliary tract cancer (BTC), covering next-generation sequencing (NGS)-identified actionable alterations, available single-gene testing alternatives when NGS access is limited, and future directions for overcoming treatment resistance and sequencing targeted drugs.
Key findings
- NGS-based extended genomic profiling identifies actionable molecular alterations in approximately half of BTC patients, with the highest incidence among those with intrahepatic cholangiocarcinoma.
- Targeted drugs have shown clinical benefit with manageable safety profiles and, despite lacking head-to-head comparison with standard second-line chemotherapy, are now recommended for fit patients after progressing on first-line palliative systemic therapy.
- The review discusses single-gene testing alternatives when NGS is unavailable, including testing priorities and yield differences, though specific comparative statistics are not given in the abstract.
Clinical relevance
The findings suggest that molecular testing (NGS where available, or targeted single-gene panels otherwise) should be considered for fit BTC patients progressing after first-line therapy, as it may identify actionable alterations that qualify them for targeted treatment, while acknowledging the current lack of randomized comparative data against chemotherapy.
Who should care
Limitations
The review explicitly notes the lack of head-to-head comparison between targeted drugs and standard second-line chemotherapy for BTC.
About half of biliary tract cancer patients have actionable mutations detectable by sequencing, and targeted therapies for these are now recommended after first-line treatment despite lacking direct comparison trials against chemotherapy.
This is an AI-generated summary of the published abstract, not a clinical recommendation. It may not reflect the full text or subsequent updates — verify against the original source before acting on it.
Abstract
The development of Next-Generation Sequencing (NGS) techniques for extended genomic profiling has led to the identification of actionable molecular alterations in approximately half of the patients with biliary tract cancer (BTC), with the highest incidences among those with intrahepatic cholangiocarcinoma. Targeted drugs have demonstrated the ability to confer clinical benefit while maintaining a manageable safety profile. As a result, despite the lack of a head-to-head comparison with standard second-line chemotherapy, they are now recommended for patients with advanced disease who are still fit after progression to first-line palliative systemic anti-cancer treatment. In this review, we will contextualize the results observed with targeted drugs in clinical trials within the framework of clinical practice. We will provide an overview of available single-gene analyses that should be considered in case of lack of access to NGS, defining testing priorities, differences in yields, and therapeutic implications. Lastly, we will discuss future perspectives in the field of precision medicine for BTC, focusing on new strategies to overcome treatment resistance, on the optimal collocation of targeted drugs in the treatment algorithm, and on newly identified actionable alterations for which compounds are currently under investigation.
DOI
10.1097/hep.0000000000001541
PMID
40982790
PMCID
PMC13585164
Research metadata (titles, abstracts, authors, publication dates) is sourced from Europe PMC, which aggregates content from PubMed/MEDLINE, PubMed Central, and other providers under the U.S. National Library of Medicine (NLM/NCBI). NLM does not claim copyright on abstracts; the original journal publishers or authors may hold rights to the full articles. AI-generated summaries are derived only from the abstract, never the full text, and are always labeled as AI-generated.
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