Nishida Naoshi
Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University Osaka 589-8511, Japan.
Cancers (Basel). 2025 Apr 6;17(7):1243. doi: 10.3390/cancers17071243.
Cholangiocarcinoma (CCA) is an aggressive malignancy with limited methods for early detection, necessitating the development of reliable biomarkers for diagnosis and management. However, conventional tumor markers, such as CA19-9 and CEA, exhibit insufficient diagnostic accuracy. Recent advancements in molecular genetics have identified several actionable mutations in CCA, enabling molecularly targeted therapies that improve survival in patients harboring these genetic alterations. Cancer panels, which facilitate multiplex genetic profiling, are critical for identifying these mutations. Studies indicate that several actionable mutations are detected in CCA cases, with patients receiving mutation-guided therapies achieving markedly better outcomes. Liquid biopsies, including cell-free DNA and circulating tumor DNA, offer real-time, non-invasive approaches to monitoring tumor dynamics, heterogeneity, and treatment responses. Furthermore, numerous studies have identified non-coding RNAs in serum and bile as promising biomarkers for the diagnosis and management of CCA. On the other hand, immunotherapy, particularly immune checkpoint inhibitors, has shown efficacy in subsets of CCA patients. However, the success of these therapies is often affected by the status of the tumor immune microenvironment (TME), underscoring the need for comprehensive TME analysis to predict responses to immune checkpoint inhibitors. Despite these advances, no single biomarker currently demonstrates sufficient sensitivity or specificity for clinical application. The integration of multi-omics approaches with cutting-edge technologies holds promise for enhancing diagnostic accuracy, optimizing treatment stratification, and advancing precision medicine in CCA. These developments highlight the transformative potential of biomarkers to improve early detection, prognostic assessment, and personalized therapeutic interventions for CCA.
胆管癌（CCA）是一种侵袭性恶性肿瘤，早期检测方法有限，因此需要开发可靠的生物标志物用于诊断和治疗。然而，传统的肿瘤标志物，如CA19-9和CEA，诊断准确性不足。分子遗传学的最新进展已在CCA中鉴定出几种可操作的突变，从而实现了分子靶向治疗，提高了携带这些基因改变的患者的生存率。有助于进行多重基因分析的癌症检测板对于识别这些突变至关重要。研究表明，在CCA病例中检测到几种可操作的突变，接受突变指导治疗的患者取得了明显更好的结果。液体活检，包括游离DNA和循环肿瘤DNA，提供了实时、非侵入性的方法来监测肿瘤动态、异质性和治疗反应。此外，许多研究已将血清和胆汁中的非编码RNA鉴定为CCA诊断和治疗的有前景的生物标志物。另一方面，免疫疗法，特别是免疫检查点抑制剂，已在部分CCA患者中显示出疗效。然而，这些疗法的成功往往受到肿瘤免疫微环境（TME）状态的影响，这突出了全面分析TME以预测对免疫检查点抑制剂反应的必要性。尽管取得了这些进展，但目前尚无单一生物标志物对临床应用表现出足够的敏感性或特异性。多组学方法与前沿技术的整合有望提高诊断准确性、优化治疗分层并推动CCA的精准医学发展。这些进展凸显了生物标志物在改善CCA的早期检测、预后评估和个性化治疗干预方面的变革潜力。
