Selected platinum complexes in standard and modern anti-cancer therapies

Abstract

The constantly observed increase in the number of cancer cases inspires research aimed at searching for new compounds with anti-cancer potential. In recent years, much research has focused on platinum complexes, especially their anti-cancer properties. Platinum derivatives are characterized by high cytotoxic activity against many types of cancer cells. However, among the numerous developed complexes, only cisplatin, carboplatin and oxaliplatin have found wide application in chemotherapeutic treatment. Nedaplatin, lobaplatin and heptaplatin have also gained recognition, and have been implemented in oncological therapy in Japan, China and Korea. Some of the platinum complexes are still at the stage of pre-clinical and clinical trials. The aim of the research conducted today is to search for platinum compounds that show high pharmacological effectiveness, with clearly limited side effects. In future therapeutic strategies, the possibility of using platinum complexes in conjunction with other chemotherapeutic compounds is being considered, which may contribute to increasing the efficacy of anti-cancer therapy.

Cisplatin in Ovarian Cancer Treatment—Known Limitations in Therapy Force New Solutions

“…Due to the number of side effects and the growing resistance phenomenon, there is an intensive sought for cisplatin analogs, which would be characterized by cytotoxic properties similar to cisplatin, but would be devoid of disadvantages limiting their widespread use. Currently, carboplatin and oxaliplatin are approved for treatment worldwide, and nedaplatin, heptaplatin and lobaplatin are in clinical trials [85]. A summary of approved and under-trial cisplatin analogs and their possible application is presented in Table 2.…”

“…Carboplatin is a second-generation platinum compound, introduced for the treatment of cancer in 1989 [85,86]. Its chemical structure is partially similar to the structure of cisplatin; however, in the place of chlorine atoms, there is an anion of cyclobutane-1,1dicarboxylic acid (Figure 3).…”

“…After entering the cell, the cyclobutane-1,1-dicarboxylic acid anion is replaced by a water molecule (just like the chlorine atoms in cisplatin), which activates the drug. The mechanism of action of carboplatin is analogous to the mechanism of action of cisplatin-the drug binds with nitrogenous bases in DNA, causing the formation of adducts, leading to DNA damage, which, in turn, results in the inhibition of replication and transcription processes, and finally cell apoptosis [85,87,88]. Both the cellular activation of carboplatin and its binding to DNA occur much slower than in the case of cisplatin, which, on the one hand, reduces the toxic side effects and ensures better tolerance of the drug by patients, but, on the other hand, reduces the effectiveness of the drug compared to cisplatin, resulting in the need of its higher doses [85,89].…”

“…Its structure is similar to that of carboplatin, but in place of the amine ligands, there is a 1,2-diaminocyclohexane group (Figure 3). The mechanism of action of oxaliplatin is the same as the mechanism of action of cisplatin and carboplatin and involves the formation of adducts with DNA [85,90]. This drug shows significantly lower systemic toxicity than cisplatin, but unfortunately also lower anticancer efficacy, which means that it is mainly used in combination with other chemotherapeutic drugs [91][92][93].…”

“…The great advantage of the drug is the lack of nephrotoxicity, and its cytotoxic effect is similar to that of carboplatin [85]. Clinical studies have shown that nedaplatin is highly effective in the treatment of ovarian cancer recurrences previously treated with cisplatin [85,94].…”