Revisiting metallodrugs for the treatment of skin cancers

Abstract

Metallodrugs were classically screened against skin cancer (either in vitro or in vivo) at the peak of the development of platinum anticancer agents. New systematic studies appeared in the past two decades. Herein, we cover the most recent literature concerning metal complexes in the treatment of skin cancers, including in vitro, in vivo and clinical data. We have compiled the antitumoral potency for each compound in every skin cancer cell line originally tested in a table. This smart table has been deposited in the open access repository Zenodo and it can be accessed at https://zenodo.org/record/5055531. Structure-activity relationships based on a careful analysis of the literature and databases allowed us to discuss possible lead coordination complexes for skin cancer chemotherapy. Additionally, recent advances were made in the understanding of skin composition, photodynamic therapies, immunological responses elicited by metals and the molecular mechanisms of skin cancers. Skin carcinomas represent an excellent prototype for looking into and developing metallodrug-based photodynamic therapy (PDT) strategies and the most recent developments towards that purpose are also covered here. With the substantial advances gained in those areas, we believe this is the perfect moment for revisiting metallodrugs as viable alternatives for the treatment of skin cancers, and how to introduce selectivity. In this context, we explore the major advances made in understanding the unique chemical composition of the outer layers of the skin and alterations observed in keratinocyte carcinomas (KCs) and melanoma as new strategies for designing selective metallodrugs against skin cancers. Signalling pathways unique to either KCs or melanoma are also explored.