In pursuit of new therapeutic strategies to fight the cancer and the development of multidrug-resistant (MDR) and extensively drug-resistant (XDR) forms of the diseases, which represent one of the most demanding public health challenge worldwide, the most urgent clinical need is to discover potent agents capable of treating MDR and XDR cancer with a success rate comparable to that of current therapies for drug-susceptible cancer. The last two decades have witnessed the discovery of new agent classes for the treatment of cancers, nearly all of which are based on organic structures including the clinically-used or currently in clinical trials. However, given the low success rate of drug candidates during clinical development and the emergence of drug resistance, the discovery of additional clinical candidates is clearly needed. Since the discovery of cisplatin, the most-commonly used inorganic drug for cancer therapy in 1970s, there is not another inorganic therapeutic developed until now.Here we report on a promising class of molecular vanadium cluster compounds (VPOM) that block cancer growth by targeting the DNA replication. The optimized VPOM-6 inhibited the growth of MDR and XDR cancer on cell level in the low micromolar range and was efficacious in a mouse model of cancer at a dose comparable to that of cisplatin (less than 20 �mol per kg body weight), which highlights the potency of this compound. In addition, VPOM-6 displays pharmacokinetic and safety profiles compatible with twice-weekly dosing and shows no hints of organ toxicity including the nephrotoxicity, which is the major dose-limiting toxicity of cisplatin. Together, our data indicate that VPOM-6 is a promising new clinical candidate for the treatment of cancer.

Discovery of a nanoscale polyvanadate, a potent clinical candidate for the treatment of cancer

248th National Meeting (2014)

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