Clinical studies of reversal of drug resistance based on glutathione.
Chem Biol Interact
; 111-112: 213-24, 1998 Apr 24.
Article
em En
| MEDLINE
| ID: mdl-9679556
ABSTRACT
The greater affinity of electrophiles for thiol groups than for hydroxyl or amine groups provides a teleological basis for the evolution of this mechanism to assist in the maintenance of cellular homeostasis. As the most abundant cellular non-protein thiol, glutathione (GSH) is pivotal in the protection of cells from electrophiles created during normal respiration and protection after exposure to environmental mutagens. Mutagens and many anti-cancer drugs, e.g. cisplatin and alkylating agents, have the same target, i.e. DNA. This suggested that one mechanism by which cancer cells might circumvent the action of cancer chemotherapeutic agents would be by increasing their cellular GSH and/or enhanced conjugation of these drugs to this abundant tripeptide. This chapter describes the abundant preclinical data that support this mechanism of resistance to platinum drugs and alkylating agents. This data was the rationale for the development of pharmacologic strategies to lower GSH and inactivate the gluathione-S-transferases to make anti-cancer drugs more effective. The positive outcome of preclinical studies to lower GSH and enhance the activity of melaphalan are described as is the status of on going clinical trials built around this data.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Resistência a Medicamentos
/
Glutationa
/
Antineoplásicos
Limite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Chem Biol Interact
Ano de publicação:
1998
Tipo de documento:
Article
País de afiliação:
Estados Unidos