Molecular Landscape and Treatment Paradigms of Hepatocellular and Cholangiocarcinoma: A Multinational Review

Abstract

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) represent the most prevalent primary liver cancers and pose significant challenges in oncology. While their etiology and incidence vary globally, the molecular landscape of these tumors is increasingly understood, offering new opportunities for precision medicine. In this joint multinational review, we present a comprehensive analysis of the key molecular pathways involved in the pathogenesis of HCC and CCA, highlighting actionable targets for emerging therapies. Recent advances in molecular diagnostics have significantly influenced treatment paradigms for both cancers. In HCC, while genetic alterations have not yet led to established diagnostic or therapeutic applications, targeting vascular endothelial growth factor (VEGF), immune checkpoints, and tyrosine kinase pathways has demonstrated considerable therapeutic potential. In CCA, genetic profiling has uncovered actionable alterations, such as FGFR2 fusions and IDH1 mutations, driving the development of targeted therapies. The growing complexity of precision oncology underscores the need for standardized molecular testing and streamlined diagnostic workflows to ensure timely and effective treatment. This review also emphasizes the importance of collaborative efforts between clinicians, pathologists, and oncologists to optimize outcomes. By synthesizing the latest molecular insights and treatment trends, this review provides a valuable resource to guide the personalized management of HCC and CCA.

Zusammenfassung

Das hepatozelluläre Karzinom (HCC) und das Cholangiokarzinom (CCA) gehören zu den häufigsten primären Leberkarzinomen und stellen eine erhebliche onkologische Herausforderung dar. Während Ätiologie und Inzidenz weltweit unterschiedlich sind, liefert ein besseres Verständnis der molekularen Grundlagen dieser Tumoren neue Ansätze für die Präzisionsmedizin. In dieser gemeinsamen multinationalen Übersichtsarbeit analysieren wir die zentralen molekularen Signalwege, die an der Pathogenese von HCC und CCA beteiligt sind, und beleuchten gezielt nutzbare Therapieansätze. Jüngste Fortschritte in der molekularen Diagnostik haben die Behandlungsstrategien für beide Tumorarten verändert. Beim HCC haben genetische Alterationen bislang zwar noch keinen festen Platz in der Diagnostik oder Therapie, jedoch zeigt die gezielte Hemmung des vaskulären endothelialen Wachstumsfaktors (VEGF), von Immun-Checkpoints und Tyrosinkinase-Signalwegen vielversprechendes therapeutisches Potenzial. Beim CCA ermöglicht die genetische Analyse die Identifikation nutzbarer Mutationen wie FGFR2-Fusionen und IDH1-Mutationen, die gezielte Therapien vorantreiben. Die zunehmende Komplexität der Präzisionsonkologie erfordert standardisierte molekulare Tests und optimierte Diagnostikabläufe, um eine rechtzeitige und effektive Behandlung sicherzustellen. Diese Übersichtsarbeit betont die Bedeutung einer interdisziplinären Zusammenarbeit zwischen Klinikern, Pathologen und Onkologen, um Behandlungsergebnisse zu verbessern. Durch die Zusammenführung aktueller molekularer Erkenntnisse und Therapieentwicklungen bietet diese Übersichtsarbeit eine wertvolle Grundlage für die personalisierte Behandlung von HCC und CCA.

Keywords

Hepatocellular Carcinoma - Cholangiocarcinoma - Molecular Targeted Therapy - Precision Medicine - Molecular Diagnostics

Schlüsselwörter

Hepatozelluläres Karzinom - Cholangiokarzinom - Präzisionsmedizin - Molekulare Diagnostik - Zielgerichtete Therapie

Publication History

Received: 21 January 2025

Accepted after revision: 24 February 2025

Article published online:
31 March 2025

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