Cisplatin in cancer treatment

Abstract

Cisplatin is a widely used chemotherapy agent in the treatment of various forms of carcinomas and sarcomas. Its effectiveness in delaying negative outcome in cancer patients has been amply documented, and attributed primarily to its ability to crosslink DNA purine bases, thus interfering with DNA repair mechanisms in cancer cells. Ultimately, this interference causes DNA damage and leads to cell apoptosis. However, the chemotherapy use of cisplatin and cisplatin-derivatives is hampered by the occurrence of major side effects in a significant percentage of cancer patients, thus limiting considerably its prolonged utilization. Acute kidney injury, gastrointestinal disorders, hemorrhage, and decreased immune response to infections are among the most common side-effects observed. On the other hand, synergistic utilization of cisplatin with other anti-cancer agents and especially its ability to induce immunomodulation in otherwise immune-depressed patients has gained significant therapeutic traction in recent times, validating the continuing clinical utilization of this agent and its derivatives. In this review, we will examine the basic physico-chemical properties of cisplatin and related derivatives, and discuss the main molecular mechanisms of actions that results in the therapeutic benefit of this class of anti-cancer agents but also in the development of major organ complications. Lastly, we will address the more recent conceptual utilization of cisplatin-induced anti-cancer immunomodulation in synergistic therapies that can also benefit of the traditional chemotherapy advantages of this class of anti-cancer agents.

Keywords: Apoptosis; Carboplatin; Cisplatin; Immune-modulation; Magnesium; Oxidative stress; Reactive oxygen species; Resistance; Toxicity.