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Cancro e complexos de platina: casos de sucesso e novas potencialidades
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Abstract(s)
O cancro corresponde a um conjunto vasto de patologias que têm em comum o crescimento celular desregulado, o que leva à formação de tumores que invadem tecidos adjacentes ou distantes, através de diversos mecanismos de transporte.
Atualmente, o grupo de doenças designadas por cancro é uma das principais causas de morte a nível global, sendo que o seu tratamento continua a ser um desafio.
Desde as últimas décadas do sec. XX que se tem assistido a um desenvolvimento notável no que diz respeito ao tratamento deste tipo de patologias, quer em termos cirúrgicos, quer na descoberta de novos fármacos e de novas estratégias de abordar a doença. Invariavelmente, o tratamento do cancro não é isento de efeitos secundários significativos e a sua eficácia depende de diversos fatores que incluem o tipo de cancro, o estádio da doença, o tipo de fármaco, o ganho de resistência ao fármaco, bem como características do próprio indivíduo.
A descoberta da cisplatina em 1968 e posterior aprovação para o tratamento tumoral, levou a uma vasta investigação envolvendo diversas classes de complexos de platina. No entanto até ao presente, apenas um reduzido número justificou a aprovação para uso clínico.
Nos anos mais recentes tem ressurgido o interesse pelos complexos de platina, sendo que os complexos de Pt (IV) têm mostrado resultados bastante promissores. Estes complexos são considerados pró-fármacos e, sendo cineticamente mais inertes do que os complexo de Pt (II), espera-se que apresentem menores efeitos secundários. A forma ativa resulta da eliminação redutiva de dois ligandos levando à formação do complexo de Pt (II), sendo que os ligandos eliminados podem também desempenhar um papel importante no mecanismo de atuação do fármaco.
Ao longo desta monografia é dada uma visão geral da investigação e uso de diversas classes de complexos de platina no tratamento tumoral, sendo abordados exemplos que ilustram as diferentes características e potencialidades destes complexos.
Cancer corresponds to a vast set of pathologies that have in common unregulated cells growth leading to tumors that invade adjacent or distant tissues, through various transport mechanisms. Currently, the group of diseases designated as cancer is one of the main causes of death on a global level, and its treatment remains a challenge. Since the last decades of the twentieth century, there has been a remarkable development in the treatment of this type of pathologies, both in surgical terms and in the discovery of new drugs and new strategies to address the disease. Notwithstanding, most cancer treatments show significant side effects and its effectiveness is driven by factors that include the type of cancer, the stage of the disease, the type of drug, the gain of resistance to the drug, as well as characteristics of the individual himself. The discovery of cisplatin in 1968 and subsequent approval for tumor treatment, led to extensive research involving several classes of platinum complexes. Since then, only a small number justified the approval for clinical use. In recent years, interest in platinum complexes has resurfaced, and Pt (IV) complexes have shown very promising results. These complexes are considered pro-drugs and, being kinetically more inert than Pt (II) complexes, they are expected to present less side effects. The active form results from the reductive elimination of two ligands leading to the formation of the Pt (II) complex, and the eliminated ligands may also play an important role in the mechanism of action of the drug. Throughout this monograph an overview is given of the investigation and use of various classes of platinum complexes in tumor treatment, with examples illustrating the different characteristics and potentials of these complexes.
Cancer corresponds to a vast set of pathologies that have in common unregulated cells growth leading to tumors that invade adjacent or distant tissues, through various transport mechanisms. Currently, the group of diseases designated as cancer is one of the main causes of death on a global level, and its treatment remains a challenge. Since the last decades of the twentieth century, there has been a remarkable development in the treatment of this type of pathologies, both in surgical terms and in the discovery of new drugs and new strategies to address the disease. Notwithstanding, most cancer treatments show significant side effects and its effectiveness is driven by factors that include the type of cancer, the stage of the disease, the type of drug, the gain of resistance to the drug, as well as characteristics of the individual himself. The discovery of cisplatin in 1968 and subsequent approval for tumor treatment, led to extensive research involving several classes of platinum complexes. Since then, only a small number justified the approval for clinical use. In recent years, interest in platinum complexes has resurfaced, and Pt (IV) complexes have shown very promising results. These complexes are considered pro-drugs and, being kinetically more inert than Pt (II) complexes, they are expected to present less side effects. The active form results from the reductive elimination of two ligands leading to the formation of the Pt (II) complex, and the eliminated ligands may also play an important role in the mechanism of action of the drug. Throughout this monograph an overview is given of the investigation and use of various classes of platinum complexes in tumor treatment, with examples illustrating the different characteristics and potentials of these complexes.
Description
Keywords
Cancro Quimioterapia Cisplatina Complexos de platina (II) Complexos de platina (IV)