Oxaliplatin and its derivatives – An overview

Abstract

Oxaliplatin was the third Pt-based anticancer drug to be clinically used worldwide. It exhibits a broad spectrum of anticancer activity and was the first to be approved for the treatment of colorectal cancer. Significantly oxaliplatin can induce immunogenic cell death and cytotoxicity via nucleolar stress in addition to established Pt(II) DNA damage responses. In this review, we describe oxaliplatin’s discovery, its properties and how it is administered as an anticancer agent. We provide an account of the current understanding of its mechanisms of action and resistance, which is essential background information for any medicinal inorganic chemist interested in designing and developing oxaliplatin derivatives, or indeed novel classes of Pt-based drugs. Furthermore we provide key examples of recent strategies employed to enhance oxaliplatin’s ability to overcome resistance, improve its specificity for cancer cells and improve Pt accumulation at the sites of tumors. In doing so we cover recent examples of (i) Pt(II) oxaliplatin derivatives, (ii) functionalised Pt(IV) oxaliplatin derivatives, (iii) photoactivatable oxaliplatin derivatives, (iv) oxaliplatin probes and (v) delivery platforms to enhance oxaliplatin accumulation. Oxaliplatin is certainly a unique member of the Pt-based anticancer class of chemotherapeutics. Continued research is required to improve our understanding of this important anticancer drug and to develop new classes of more effective selectively delivered analogues that overcome Pt resistance.