Vall d'Hebron Institute of Oncology and Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
Target Oncol. 2018 Dec;13(6):691-704. doi: 10.1007/s11523-018-0609-7.
Only a limited number of therapeutic strategies are available for patients diagnosed with pancreatic adenocarcinoma, and disease recurrence and mortality are consequently high. For metastatic disease, two combinations are approved in the first line setting: a triplet with 5-fluoruracil, irinotecan, and oxaliplatin, and the combination of gemcitabine and nab-paclitaxel. In patients who have progressed on gemcitabine, a new nanoliposomal formulation of irinotecan has recently been approved. While these treatments have demonstrated some efficacy, there has been little increase in survival rates for metastatic pancreatic cancer patients. Consequently, there is an urgent need for research and development of new treatments. As there is now a deeper understanding of pancreatic cancer biology, new drugs targeting altered pathways are under research, including agents that target TGF-β, IGF, or NOTCH. Furthermore, taking into account the role of the tumor stroma in this disease, some stroma-targeting drugs are being developed, including PEGPH20, a pegylated recombinant human hyaluronidase. In the immunotherapy field, although checkpoint inhibitors have failed to demonstrate benefit as monotherapies, combinations with other drugs are being investigated, with promising preliminary results. Other strategies under research are targeting tumor metabolism or DNA repair deficiency.
只有有限数量的治疗策略可用于诊断为胰腺腺癌的患者，因此疾病复发和死亡率很高。对于转移性疾病，一线治疗有两种联合方案获批：一种是氟尿嘧啶、伊立替康和奥沙利铂的三联方案，另一种是吉西他滨和nab-紫杉醇的联合方案。在吉西他滨治疗进展的患者中，最近批准了一种伊立替康的新型纳米脂质体制剂。尽管这些治疗方法已经显示出一定的疗效，但转移性胰腺癌患者的生存率几乎没有提高。因此，迫切需要研究和开发新的治疗方法。由于现在对胰腺癌生物学有了更深入的了解，正在研究针对改变途径的新药，包括针对 TGF-β、IGF 或 NOTCH 的药物。此外，考虑到肿瘤基质在这种疾病中的作用，正在开发一些针对基质的药物，包括 PEGPH20，一种聚乙二醇化重组人透明质酸酶。在免疫治疗领域，尽管检查点抑制剂作为单一疗法未能显示出获益，但正在研究与其他药物的联合治疗方案，初步结果令人鼓舞。其他正在研究的策略包括靶向肿瘤代谢或 DNA 修复缺陷。
