Cholangiocarcinomas (CCA) pose a complex challenge in oncology due to diverse etiologies, necessitating tailored therapeutic approaches. This review discusses the risk factors, molecular pathology, and current therapeutic options for CCA and explores the emerging strategies encompassing targeted therapies, immunotherapy, novel compounds from natural sources, and modulation of gut microbiota. CCA are driven by an intricate landscape of genetic mutations, epigenetic dysregulation, and post-transcriptional modification, which differs based on geography (e.g., for liver fluke versus non-liver fluke-driven CCA) and exposure to environmental carcinogens (e.g., exposure to aristolochic acid). Liquid biopsy, including circulating cell-free DNA, is a potential diagnostic tool for CCA, which warrants further investigations. Currently, surgical resection is the primary curative treatment for CCA despite the technical challenges. Adjuvant chemotherapy, including cisplatin and gemcitabine, is standard for advanced, unresectable, or recurrent CCA. Second-line therapy options, such as FOLFOX (oxaliplatin and 5-FU), and the significance of radiation therapy in adjuvant, neoadjuvant, and palliative settings are also discussed. This review underscores the need for personalized therapies and demonstrates the shift towards precision medicine in CCA treatment. The development of targeted therapies, including FDA-approved drugs inhibitingFGFR2gene fusions andIDH1mutations, is of major research focus. Investigations into immune checkpoint inhibitors have also revealed potential clinical benefits, although improvements in survival remain elusive, especially across patient demographics. Novel compounds from natural sources exhibit anti-CCA activity, while microbiota dysbiosis emerges as a potential contributor to CCA progression, necessitating further exploration of their direct impact and mechanisms through in-depth research and clinical studies. In the future, extensive translational research efforts are imperative to bridge existing gaps and optimize therapeutic strategies to improve therapeutic outcomes for this complex malignancy.
胆管癌因其病因多样，在肿瘤学领域构成复杂挑战，需采取个体化治疗策略。本综述探讨胆管癌的危险因素、分子病理学及当前治疗方案，并展望靶向治疗、免疫疗法、天然来源新型化合物及肠道菌群调控等新兴策略。胆管癌的发生涉及基因突变、表观遗传失调和转录后修饰的复杂机制，其驱动因素因地域差异（如肝吸虫感染与非肝吸虫相关胆管癌）及环境致癌物暴露（如马兜铃酸接触）而不同。液体活检（包括循环游离DNA检测）作为潜在诊断工具值得深入研究。目前手术切除仍是主要根治手段，尽管存在技术挑战。顺铂联合吉西他滨的辅助化疗已成为晚期、不可切除或复发性胆管癌的标准方案。本文同时探讨二线治疗方案（如FOLFOX方案中的奥沙利铂联合5-氟尿嘧啶）及放疗在辅助、新辅助和姑息治疗中的价值。本综述强调个体化治疗的必要性，揭示胆管癌治疗向精准医学的转变趋势。靶向治疗研发（包括FDA批准的FGFR2基因融合和IDH1突变抑制剂）已成为研究重点。免疫检查点抑制剂虽显示出临床潜力，但在改善患者生存率方面仍面临挑战，特别是在不同人群中的疗效差异。天然来源新型化合物展现出抗胆管癌活性，而菌群失调可能促进疾病进展，需通过深入研究和临床试验进一步探索其直接作用机制。未来必须开展大量转化研究以弥补现有不足，优化治疗策略，从而改善这一复杂恶性肿瘤的临床结局。
Cholangiocarcinoma: Recent Advances in Molecular Pathobiology and Therapeutic Approaches
肿瘤(癌症)患者之家