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，其早期检测手段有限，亟需开发可靠的生物标志物用于诊断和治疗管理。然而，传统肿瘤标志物如CA19-9和CEA的诊断准确性不足。分子遗传学的最新进展已识别出胆管癌中多个可干预的基因突变，使得针对这些遗传改变进行分子靶向治疗成为可能，从而改善了携带相关突变患者的生存状况。癌症基因检测组合通过实现多重基因分析，对识别这些突变至关重要。研究表明，在胆管癌病例中可检测到多个可干预突变，接受突变指导治疗的患者预后显著改善。液体活检技术（包括游离DNA和循环肿瘤DNA检测）为实时、无创监测肿瘤动态、异质性及治疗反应提供了新途径。此外，多项研究已发现血清和胆汁中的非编码RNA可作为胆管癌诊断和管理的潜在生物标志物。另一方面，免疫治疗（特别是免疫检查点抑制剂）在部分胆管癌患者中显示出疗效。但这些疗法的成功常受肿瘤免疫微环境（TME）状态的影响，这凸显了进行全面TME分析以预测免疫检查点抑制剂反应的必要性。尽管取得这些进展，目前尚无单一生物标志物具备临床转化所需的足够敏感度或特异度。多组学方法与前沿技术的整合有望提升诊断准确性、优化治疗分层，并推动胆管癌精准医疗的发展。这些进展突显了生物标志物在改善胆管癌早期检测、预后评估和个体化治疗干预方面的变革潜力。
Biomarkers and Management of Cholangiocarcinoma: Unveiling New Horizons for Precision Therapy
肿瘤(癌症)患者之家