Accepted for/Published in: JMIR Research Protocols
Date Submitted: Sep 7, 2024
Date Accepted: Apr 1, 2025
Identification of compounds with potential to act as dual drug efflux pump inhibitors in resistant cancer cells and bacteria – a systematic review protocol
ABSTRACT
Background:
Drug efflux mediated by transporter proteins is one of the major mechanisms conferring resistance to antimicrobial agents in bacteria and multidrug resistance (MDR) in cancer cells. Therefore, development or identification of efflux modulators represents a promising strategy to overcoming the resistant phenotype. Various chemical compounds have been tested in experimental studies as reversal agents either in combination with antibiotics or with chemotherapy and have shown sensitizing activity in resistant bacteria or cancer cell lines. Owing to the common resistance mechanisms exhibited by bacteria and cancer cells, identification of chemical agents with dual reversal activity represents a strategy to combat antimicrobial and cancer multidrug resistance.
Objective:
We will conduct a systematic review to identify compounds that have shown activity in reversing antimicrobial as well as cancer multidrug resistance mediated by drug efflux pumps and to summarize their structural and biological parameters responsible for the interaction with drug efflux pumps.
Methods:
We will search PubMed and Scopus databases for full-text peer-reviewed journal articles in English language published between January 2012 and June 2024. Only studies from in vitro experiments will be analyzed, if they employ methods to detect change in antibiotic sensitivity and chemosensitivity of resistant bacteria and cancer cells upon treatment with an efflux pump inhibitor. Study selection, data extraction and risk of bias assessment will be performed by two independent reviewers. Main data elements will include structural identifier of the tested inhibitor, bacterial strain, cancer cell line, methods proving reversal activity, half maximal inhibitory concentration and other relevant quantitative estimates of reversal activity. Data synthesis will be performed as a narrative summary and content will be curated in tabular and graphical form.
Results:
We anticipate that results from this study will outline the potential of various compounds to act as dual chemosensitizers and reverse both antimicrobial and cancer multidrug resistance.
Conclusions:
Our review will highlight the overlap between efflux pumps inhibition as a strategy to combat MDR in both bacterial and cancer cells and it will provide structured data for rational drug design of dual efflux pump inhibitors.
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