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Study of glutathione S-transferase inhibitors and their potential role in ameliorating the resistance to the electrophilic chemotherapeutic agent Busulfan

ContributorsRobin, Shannon
Master program titleMaîtrise universitaire (Master) en Biologie (orientation libre)
Defense date2020
Abstract

Hematologic malignancies are the most frequent cancers in the pediatric population. Despite the high cure rate, treatments are highly toxic on the long-term basis, damaging different organ systems. In addition, medications do not display the same efficacy in every patient. Some of them do not respond at all, leading to possible therapeutic failure. Improving quality of life of the patients by reducing treatment-related toxicities (TRTs) and increasing the effectiveness of already existing drugs is an important field of research that requires special attention. Busulfan is one of the alkylating agents used in the myeloablative conditioning regimen prior to hematopoietic stem-cell transplantation (HSCT), a medical procedure to treat blood cancers. The enzymatic family of glutathione S-transferases (GSTs) is responsible for the metabolism of this medication and other electrophilic chemotherapeutic drugs. As reported in the literature, there is an association between genotypes of GSTs subtypes and TRTs after infusion with electrophilic agents. In addition, an overexpression of GSTs in tumor tissues is associated with chemotherapeutic drug resistance. Besides their role as detoxifier, GSTs regulate mitogen-activated phosphate kinase (MAPK) pathways. Considering these two roles, the main biological hypothesis is that the use of a drug combination, constituted of Busulfan and a GST inhibitor will increase the efficacy of the alkylating agent.

eng
Keywords
  • Glutathione S-transferase
  • Busulfan
  • Ethacrynic acid
  • Curcumin
  • Leukemia
  • GST inhibitors
Citation (ISO format)
ROBIN, Shannon. Study of glutathione S-transferase inhibitors and their potential role in ameliorating the resistance to the electrophilic chemotherapeutic agent Busulfan. 2020.
Main files (1)
Master thesis
accessLevelRestricted
Identifiers
  • PID : unige:130491
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Creation2020/02/05 12:05:00
First validation2020/02/05 12:05:00
Update time2023/03/15 21:07:47
Status update2023/03/15 21:07:47
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