Kang Sandra, El-Rayes Bassel F, Akce Mehmet
Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA.
Department of Internal Medicine, Division of Hematology and Oncology, O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL 35233, USA.
Cancers (Basel). 2022 Mar 29;14(7):1748. doi: 10.3390/cancers14071748.
Biliary tract cancers (BTC) comprise a rare and diverse group of malignancies that involve the gallbladder and biliary tree. These cancers typically present in later stages because they are aggressive in nature and affected patients are often asymptomatic in earlier stages of disease. Moreover, BTCs are generally refractory to cytotoxic chemotherapy, which further contributes to their associated poor survival outcomes. Novel therapy approaches are clearly needed. Molecular targeted agents have been developed based on our expanding knowledge of the genetic mutations underlying BTCs and represent a promising treatment strategy in molecularly selected subgroups of patients. In addition, the advent of immunotherapy over recent years has dramatically changed the bleak outcomes observed in malignancies such as melanoma. Our growing understanding of the complex tumor microenvironment in BTC has identified mechanisms of tumor immune evasion that could potentially be targeted with immunotherapy. As a result, different immunotherapeutic approaches including immune checkpoint inhibitors, cancer vaccines, and adoptive cell therapy, have been investigated. The use of immunotherapeutic agents is currently only approved for a small subset of treatment-refractory BTCs based on microsatellite instability (MSI) status and tumor mutational burden (TMB), but this will likely change with the potential approval of immunotherapy plus chemotherapy as a result of the TOPAZ-1 trial.
胆道癌（BTC）是一组罕见且多样的恶性肿瘤，包括胆囊癌和胆管癌。这些癌症通常在晚期出现，因为它们本质上具有侵袭性，且患病患者在疾病早期往往没有症状。此外，BTC通常对细胞毒性化疗耐药，这进一步导致了其较差的生存结局。显然需要新的治疗方法。基于我们对BTC潜在基因突变的不断了解，已经开发出分子靶向药物，这在经过分子筛选的部分患者亚组中是一种有前景的治疗策略。此外，近年来免疫疗法的出现极大地改变了黑色素瘤等恶性肿瘤中观察到的严峻结局。我们对BTC复杂肿瘤微环境的日益了解，已经确定了肿瘤免疫逃逸的机制，这些机制可能是免疫疗法的潜在靶点。因此，已经对包括免疫检查点抑制剂、癌症疫苗和过继性细胞疗法在内的不同免疫治疗方法进行了研究。目前，基于微卫星不稳定性（MSI）状态和肿瘤突变负荷（TMB），免疫治疗药物仅被批准用于一小部分难治性BTC，但由于TOPAZ - 1试验，免疫疗法联合化疗有可能获批，这种情况可能会发生改变。
