The purpose of this paper is to summarize mode of action of cisplatin on the tumor cells, a brief outlook on the metallocene compounds as antitumor drugs as well as the future tendencies for the use of the latter in anticancer chemotherapy. Molecular mechanisms of cisplatin interaction with DNA, DNA repair mechanisms, and cellular proteins are discussed. Molecular background of the sensitivity and resistance to cisplatin, as well as its influence on the efficacy of the antitumor immune response was evaluated. Furthermore, herein are summarized some metallocenes (titanocene, vanadocene, molybdocene, ferrocene, and zirconocene) with high antitumor activity.

The anticancer activity of platinum complexes has been known since the discovery of classical Pt(II)‐based drug cisplatin. However, Pt(IV) complexes have greater inertness than corresponding Pt(II) complexes, thus allowing the oral administration and reducing the toxicity associated with platinum‐based chemotherapy. Here, we describe the in vitro antitumor activity of some novel Pt(IV)‐based agents against mouse fibrosarcoma L929 cells and human astrocytoma U251 cells. The cytotoxicity of 2 Pt(IV) complexes with bidentate ethylenediamine‐N,N′‐di‐3‐propanoato esters was found to be markedly higher than that of their Pt(II) counterparts and comparable to the antitumor action of cisplatin. In contrast to cisplatin, which caused oxidative stress‐independent apoptotic cell death of tumor cells, these Pt(IV) complexes induced oxygen radical‐mediated tumor cell necrosis. Importantly, the cytotoxic action of novel Pt(IV) complexes was markedly more rapid than that of cisplatin, indicating their potential usefulness in anticancer therapy.

This article reviews recent studies of platinum and other metal-containing antitumor drugs in preclinical development. A short overview of the development of cisplatin-based drug generations is given. Some pioneering strategies towards unconventional drugs, such as platinum complexes with biomolecules and carrier ligands, organoplatinum and multinuclear platinum complexes developed in recent years are outlined. Furthermore, nonplatinum-based antitumor drugs containing ruthenium(II/III), gallium(III), titanium(IV) or tin(IV) that illustrate the prominent strategies are presented with an emphasis on recent developments. In addition, alternatives for water insoluble drugs will be discussed. A brief overview of development of nanodrug delivery systems and their potential as alternative cancerostatic carriers are discussed.