Mehmood Rao Khalid, Parker Jody, Ahmed Shakil, Qasem Eyas, Mohammed Ahmed A, Zeeshan Muhammed, Jehangir Ernest
Betsi Cadwaladr University Health Board, Department of Surgery, Ysbyty Glan Clwyd, Rhyl, North Wales, LL18 5UJ, UK.
The Royal Liverpool and Broadgreen University Hospitals NHS Trust, Prescot Street, Liverpool, L7 8XP, UK.
World J Oncol. 2014 Jun;5(3):97-108. doi: 10.14740/wjon830w. Epub 2014 Jun 25.
Platinum-based chemotherapy made a paradigm shift in the treatment of different cancers initially; however, the success of these agents may have reached the peak as researchers have tried different combination regimes in different trials without having major differences in the end results. New frontiers of research were opened up firstly with this discovery that conventional chemo-radiation therapy can induce immunological cell death by recruiting high-mobility group box 1 (HMGB1) protein which triggers the T cell immunity and secondly monoclonal antibodies agents which were regrettably not effective as "monotherapy"; however, the combination with conventional chemotherapy had demonstrated good results. Different monoclonal antibodies and conventional chemotherapeutic combination regimes are currently in use and researchers are trying different other combinations as well to glean the maximum benefits from them. Several strategies conferring resistance to platinum compounds have been identified, but there is still significant research required to achieve full understanding of these resistance mechanisms to overcome the ineffectiveness or toxicities of platinum compounds. It seems reasonable in the current perspective when conventional chemotherapeutic agents exhibited immunogenic cell death and they are currently in use with monoclonal antibodies to revisit the platinum agent's pharmacology. This may discover new basis for combination chemotherapy with monoclonal antibodies which may improve the current cancer treatments by opening new vistas for newer combination regimes with less toxicity and better efficacy. In this article we review the pharmacologies of both cisplatin and oxaliplatin in the drug development perspectives and explore the possible association of these drugs with monoclonal antibodies.
基于铂的化疗最初在不同癌症的治疗中引发了范式转变；然而，随着研究人员在不同试验中尝试了不同的联合方案，而最终结果却没有重大差异，这些药物的成功可能已达到顶峰。研究的新前沿首先随着这一发现而开启，即传统的放化疗可以通过募集触发T细胞免疫的高迁移率族蛋白盒1（HMGB1）来诱导免疫细胞死亡，其次是单克隆抗体药物，遗憾的是，这些药物作为“单一疗法”并不有效；然而，与传统化疗联合使用已显示出良好效果。目前正在使用不同的单克隆抗体与传统化疗的联合方案，研究人员也在尝试其他不同的联合方案，以从中获取最大益处。已经确定了几种赋予对铂化合物耐药性的策略，但仍需要大量研究来全面了解这些耐药机制，以克服铂化合物的无效性或毒性。从当前的角度来看，当传统化疗药物表现出免疫原性细胞死亡且目前正与单克隆抗体联合使用时，重新审视铂类药物的药理学似乎是合理的。这可能会发现与单克隆抗体联合化疗的新基础，通过为毒性更小、疗效更好的新联合方案开辟新前景，从而改善当前的癌症治疗。在本文中，我们从药物研发的角度综述顺铂和奥沙利铂的药理学，并探讨这些药物与单克隆抗体之间可能的关联。
