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Sousa, Graziele Fonseca de; Wlodarczyk, Samarina Rodrigues; Monteiro, Gisele
Brazilian Journal of Pharmaceutical Sciences, 12/2014, Volume: 50, Issue: 4Journal Article
Carboplatin is a derivative of cisplatin; it has a similar mechanism of action, but differs in terms of structure and toxicity. It was approved by the FDA in the 1980s and since then it has been widely used in the treatment of several tumor types. This agent is characterized by its ability to generate lesions in DNA through the formation of adducts with platinum, thereby inhibiting replication and transcription and leading to cell death. However, its use can lead to serious inconvenience arising from the development of resistance that some patients acquire during treatment, limiting the scope of its full potential. Currently, the biochemical mechanisms related to resistance are not precisely known. Therefore, knowledge of pathways associated with resistance caused by carboplatin exposure may provide valuable clues for more efficient rational drug design in platinum-based therapy and the development of new therapeutic strategies. In this narrative review, we discuss some of the known mechanisms of resistance to platinum-based drugs, especially carboplatin. A carboplatina é um derivado da cisplatina, possuindo mecanismo de ação similar, diferindo em estrutura e toxicidade. Este fármaco foi aprovado pelo FDA em meados de 1980 e, desde então, tem sido amplamente usado no tratamento de diversos tipos de tumores. Este agente é caracterizado por sua habilidade em gerar lesões no DNA através da formação de adutos com a platina, inibindo a replicação e a transcrição, levando à morte celular. Entretanto, seu uso pode levar a graves inconvenientes, advindos do desenvolvimento de resistência que alguns pacientes adquirem durante o tratamento, limitando o alcance de seu potencial. Até então, os mecanismos bioquímicos relacionados ao problema da resistência não são precisamente conhecidos. Dessa forma, o conhecimento das vias associadas à resistência causada pela exposição à carboplatina pode prover valiosas informações para o planejamento racional de fármacos com base em platina mais eficiente e para o desenvolvimento de novas estratégias terapêuticas. Nesta revisão narrativa, serão discutidos alguns mecanismos de resistência a fármacos com base em platina, especialmente ao antitumoral carboplatina.
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