Cepeda Victoria, Fuertes Miguel A, Castilla Josefina, Alonso Carlos, Quevedo Celia, Pérez Jose M
Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Facultad de Ciencias, Universidad Autónoma de Madrid, 28049-Madrid, Spain.
Anticancer Agents Med Chem. 2007 Jan;7(1):3-18. doi: 10.2174/187152007779314044.
Since the discovery by Rosenberg and collaborators of the antitumor activity of cisplatin 35 years ago, three platinum antitumor drugs (cisplatin, carboplatin and oxaliplatin) have enjoyed a huge clinical and commercial hit. Ever since the initial discovery of the anticancer activity of cisplatin, major efforts have been devoted to elucidate the biochemical mechanisms of antitumor activity of cisplatin in order to be able to rationally design novel platinum based drugs with superior pharmacological profiles. In this report we attempt to provide a current picture of the known facts pertaining to the mechanism of action of the drug, including those involved in drug uptake, DNA damage signals transduction, and cell death through apoptosis or necrosis. A deep knowledge of the biochemical mechanisms, which are triggered in the tumor cell in response to cisplatin injury not only may lead to the design of more efficient platinum antitumor drugs but also may provide new therapeutic strategies based on the biochemical modulation of cisplatin activity.
35年前罗森伯格及其合作者发现顺铂的抗肿瘤活性以来，三种铂类抗肿瘤药物（顺铂、卡铂和奥沙利铂）在临床和商业上都取得了巨大成功。自从最初发现顺铂的抗癌活性以来，人们付出了巨大努力来阐明顺铂抗肿瘤活性的生化机制，以便能够合理设计出具有更优药理学特性的新型铂类药物。在本报告中，我们试图提供有关该药物作用机制的已知事实的现状，包括那些涉及药物摄取、DNA损伤信号转导以及通过凋亡或坏死导致细胞死亡的机制。深入了解肿瘤细胞因顺铂损伤而触发的生化机制，不仅可能导致设计出更有效的铂类抗肿瘤药物，还可能基于顺铂活性的生化调节提供新的治疗策略。
