Arias-Pinilla Gustavo A, Modjtahedi Helmout
Department of Oncology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S10 2JF, UK.
School of Life Sciences, Pharmacy and Chemistry, Kingston University London, Kingston-upon-Thames, Surrey KT1 2EE, UK.
Cancers (Basel). 2021 Apr 8;13(8):1781. doi: 10.3390/cancers13081781.
Pancreatic cancer remains as one of the most aggressive cancer types. In the absence of reliable biomarkers for its early detection and more effective therapeutic interventions, pancreatic cancer is projected to become the second leading cause of cancer death in the Western world in the next decade. Therefore, it is essential to discover novel therapeutic targets and to develop more effective and pancreatic cancer-specific therapeutic agents. To date, 45 monoclonal antibodies (mAbs) have been approved for the treatment of patients with a wide range of cancers; however, none has yet been approved for pancreatic cancer. In this comprehensive review, we discuss the FDA approved anticancer mAb-based drugs, the results of preclinical studies and clinical trials with mAbs in pancreatic cancer and the factors contributing to the poor response to antibody therapy (e.g. tumour heterogeneity, desmoplastic stroma). MAb technology is an excellent tool for studying the complex biology of pancreatic cancer, to discover novel therapeutic targets and to develop various forms of antibody-based therapeutic agents and companion diagnostic tests for the selection of patients who are more likely to benefit from such therapy. These should result in the approval and routine use of antibody-based agents for the treatment of pancreatic cancer patients in the future.
胰腺癌仍然是侵袭性最强的癌症类型之一。由于缺乏用于早期检测的可靠生物标志物以及更有效的治疗干预措施，预计在未来十年内，胰腺癌将成为西方世界癌症死亡的第二大主要原因。因此，发现新的治疗靶点并开发更有效且针对胰腺癌的治疗药物至关重要。迄今为止，已有45种单克隆抗体（mAb）被批准用于治疗多种癌症患者；然而，尚无一种被批准用于胰腺癌治疗。在这篇全面综述中，我们讨论了美国食品药品监督管理局（FDA）批准的基于抗癌单克隆抗体的药物、单克隆抗体在胰腺癌的临床前研究和临床试验结果，以及导致抗体治疗反应不佳的因素（如肿瘤异质性、促结缔组织增生性间质）。单克隆抗体技术是研究胰腺癌复杂生物学、发现新治疗靶点以及开发各种基于抗体的治疗药物和伴随诊断检测以选择更可能从此类治疗中获益患者的优秀工具。这些有望促使基于抗体的药物在未来获得批准并常规用于治疗胰腺癌患者。
