Review on pharmacology of cisplatin: Clinical use, toxicity and mechanism of resistance of cisplatin

Abstract

Cisplatin is a chemotherapeutic drug that has been used in the treatment of various types of human cancers such as ovarian, lung, head and neck, testicular and bladder. Cisplatin has demonstrated efficacy against various types of cancers such as germ cell tumors, sarcomas, carcinomas as well as lymphomas. The current study presents a pharmacological review on the drug including its mechanism of action, resistance mechanism, and toxicity as well as its clinical applications. The mechanism of action of cisplatin has been associated with ability to crosslink with the urine bases on the DNA to form DNA adducts, preventing repair of the DNA leading to DNA damage and subsequently induces apoptosis within cancer cells. However, the drug exhibits certain level of resistance including increased repair of the damaged DNA, reduction in the accumulation of the drug intracellular and cytosolic inactivation of cisplatin. The drug is also characterized by various toxic side effects including nausea, nephrotoxicity, Cardiotoxicity, hepatotoxicity and neurotoxicity. Due various side effects as well as drug resistance, other anti-cancer drugs that contain platinum such as carboplatin and oxaliplatin among others have been used in combination with cisplatin in chemotherapeutic treatment of cancer. Strong evidence from research has demonstrated higher efficacy of combination of chemotherapies of cisplatin together with other drugs in overcoming drug resistance and in reducing toxic effects as well. Future studies that explore combinational techniques that target various mechanisms such as reduction in the uptake of cisplatin as well as inflammation could enhance efficacy of cisplatin.