PDF(Pubmed)
Abstract：
To overcome the poor prognosis of cholangiocarcinoma (CCA), highly targeted therapies, such as antibody-drug conjugates (ADCs), photodynamic therapy (PDT) with/without systemic chemotherapy, and experimental photoimmunotherapy (PIT), have been developed. Three preclinical trials have investigated the use of ADCs targeting specific antigens, namely HER2, MUC1, and glypican-1 (GPC1), for CCA. Trastuzumab emtansine demonstrated higher antiproliferative activity in CCA cells expressing higher levels of HER2. Similarly, \"staphylococcal enterotoxin A-MUC1 antibody\" and \"anti-GPC1 antibody-monomethyl auristatin F\" conjugates showed anticancer activity. PDT is effective in areas where appropriate photosensitizers and light coexist. Its mechanism involves photosensitizer excitation and subsequent reactive oxygen species production in cancer cells upon irradiation. Hematoporphyrin derivatives, temoporfin, phthalocyanine-4, talaporfin, and chlorine e6 derivatives have mainly been used clinically and preclinically in bile duct cancer. Currently, new forms of photosensitizers with nanotechnology and novel irradiation catheters are being developed. PIT is the most novel anti-cancer therapy developed in 2011 that selectively kills targeted cancer cells using a unique photosensitizer called \"IR700\" conjugated with an antibody specific for cancer cells. PIT is currently in the early stages of development for identifying appropriate CCA cell targets and irradiation devices. Future human and artificial intelligence collaboration has potential for overcoming challenges related to identifying universal CCA cell targets. This could pave the way for highly targeted therapies for CCA, such as ADC, PDT, and PIT.
摘要：
为了克服胆管癌（CCA）的不良预后，具有高度针对性的治疗方法,如抗体-药物缀合物(ADC)，光动力疗法（PDT）伴/不伴全身化疗，和实验性光免疫疗法（PIT），已经开发了。三项临床前试验研究了靶向特定抗原的ADC的使用，即HER2、MUC1和磷脂酰肌醇蛋白聚糖-1(GPC1)，对于CCA。曲妥珠单抗emtansine在表达较高水平HER2的CCA细胞中表现出更高的抗增殖活性。同样，“葡萄球菌肠毒素A-MUC1抗体”和“抗GPC1抗体-单甲基奥瑞他汀F”偶联物显示抗癌活性。PDT在合适的光敏剂和光共存的区域是有效的。其机制涉及光敏剂激发和随后照射时癌细胞中活性氧的产生。血卟啉衍生物，替莫芬,酞菁-4，塔拉波芬，和氯e6衍生物主要在临床和临床前用于胆管癌。目前,正在开发具有纳米技术和新型辐照导管的新型光敏剂。PIT是2011年开发的最新颖的抗癌疗法，它使用一种名为“IR700”的独特光敏剂与癌细胞特异性抗体缀合，选择性地杀死靶向癌细胞。PIT目前处于开发的早期阶段，用于识别合适的CCA细胞靶标和辐照设备。未来的人类和人工智能合作有可能克服与识别通用CCA小区目标相关的挑战。这可以为CCA的高度靶向治疗铺平道路，比如ADC,PDT,和坑。
