Pt(iv) anticancer prodrugs bearing an oxaliplatin scaffold: what do we know about their bioactivity?

Cancer remains a significant global health challenge, necessitating continuous advancements in therapeutic strategies. Chemotherapeutic agents have long been pivotal in cancer treatment, with platinum(Pt)-based drugs holding a prominent place. Oxaliplatin, a third-generation Pt(ii) compound, has gathered attention for its efficacy towards several cisplatin-resistant cancer cells and has become the front-line therapy for metastatic colorectal cancer. However, inherent limitations such as resistance development and dose-dependent side effects like oxaliplatin-induced peripheral neuropathy (OIPN) prompt the exploration of novel derivatives. Pt(iv) prodrugs have emerged as a promising avenue in cancer therapy, exploiting the intrinsic cytotoxicity of platinum while offering enhanced stability and tunable pharmacokinetics. However, the majority of Pt(iv) prodrugs reported in the literature, for their in vitro or in vivo anticancer properties, are cisplatin-based. This comprehensive review gathers, to our knowledge, the recent advances on oxaliplatin-based Pt(iv) derivatives and how they can strategically address the aforementioned challenges.