Hallmarks of liver cancer: Therapeutic implications
Targetable genomic drivers have been identified in 45% of iCCA cases, marking a major success in precision oncology for tumors harboring activating alterations in BRAF, fibroblast growth factor receptor (FGFR), ERBB2, and isocitrate dehydrogenase 1 (IDH1).
The hallmarks of cancer, first proposed in 2000, have since provided a unified framework for understanding the complexity of carcinogenesis. This conceptual model has profoundly influenced the treatment landscape of primary liver cancer, which includes hepatocellular carcinoma (HCC, ~85%) and intrahepatic cholangiocarcinoma (iCCA, 10%) — malignancies with high mortality. Key hallmarks exhibited by HCC include sustaining proliferative signaling, inducing or accessing vasculature, and avoiding immune detection. Over the past two decades, outcomes for patients with advanced HCC have significantly improved with immunotherapies. iCCA is characterized by hallmarks such as sustaining proliferative signaling, deregulating cellular metabolism, and avoiding immune detection. Unlike HCC, roughly 45% of iCCA harbor alterations amenable to precision oncology approaches, including fibroblast growth factor receptor 2 (FGFR2) fusions, isocitrate dehydrogenase 1 (IDH1) mutations, ERBB2 alterations, and BRAF mutations. In this review, we explore how this framework has reshaped liver cancer care and discuss the resulting breakthroughs in management and emerging directions that may further improve therapeutic strategies.
Understanding the distribution of actionable genomic drivers across liver cancer subtypes informs the feasibility of precision oncology; iCCA’s higher frequency of targetable alterations has led to developing specific inhibitors, while HCC’s limited actionable landscape underscores the need for new therapeutic strategies and the importance of ongoing immunotherapy and multikinase approaches.
Bizonyítékszint: Klinikai vizsgálat. Formális klinikai vizsgálati eredmény.
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