Optimizing outcomes and personalizing care with targeted agents in advanced cholangiocarcinoma.

Autor: Mahmood U; Department of Gastrointestinal Oncology, University College Hospital NHS Foundation Trust (UCLH), London NW1 2BU, UK., Abbass A; Department of Gastrointestinal Oncology, University College Hospital NHS Foundation Trust (UCLH), London NW1 2BU, UK., Khan K; Department of Gastrointestinal Oncology, University College Hospital NHS Foundation Trust (UCLH), London NW1 2BU, UK; University College London Cancer Institute, London WC1E 6DD, UK. Electronic address: khurum.khan1@nhs.net.
Jazyk: angličtina
Zdroj: Cancer treatment reviews [Cancer Treat Rev] 2024 Dec; Vol. 131, pp. 102851. Date of Electronic Publication: 2024 Nov 05.
DOI: 10.1016/j.ctrv.2024.102851
Abstrakt: Traditional chemotherapy and immunotherapy-based systemic treatments for locally advanced or metastatic cholangiocarcinoma have been associated with poor clinical outcomes driven partly by molecular heterogeneity promoting early treatment resistance and a higher toxicity profile associated with these regimens. Few patients are eligible for upfront surgical resection and clinical studies have been traditionally difficult to conduct due to the orphan nature of this disease. However, increasing use of genomic profiling in clinical practice have led to active investigations of aberrant albeit promising mechanistic therapeutic targets such as IDH-1, FGFRs, BRAF V600E , HER-2 and NTRK. This review article aims to highlight the complex genomic landscape of this difficult-to-treat disease, followed by a discussion of evidence-based biological mechanisms that can be actioned using targeted agents. We explore the clinical rationale behind a targeted therapeutic strategy, the role of liquid biopsies in guiding clinical decisions and future treatment pathways for cholangiocarcinoma management. We also discuss the challenges and opportunities originating from recent clinical trials evaluating targeted treatments and our own institutional experience at UCLH that have aimed to address some of these biological complexities and have translated into improved patient outcomes via effective molecularly driven patient selection strategies. We also provide perspectives on emerging novel, next generation targeted inhibitors overcoming treatment resistance to previous targeted agents with demonstrated clinical value in a challenging patient population.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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