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Selection of clinically relevant drug concentrations for in vitro studies of candidates drugs for cancer repurposing: a proposal

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Abstract

Drug repurposing of widely prescribed patent-off and cheap drugs may provide affordable drugs for cancer treatment. Nevertheless, many preclinical studies of cancer drug repurposing candidates use in vitro drug concentrations too high to have clinical relevance. Hence, preclinical studies must use clinically achievable drug concentrations. In this work, several FDA-approved cancer drugs are analyzed regarding the correlation between the drug inhibitory concentrations 50% (IC50) tested in cancer cell lines and their corresponding peak serum concentration (Cmax) and area under the curve (AUC) reported in clinical studies of these drugs. We found that for most targeted cancer drugs, the AUC and not the Cmax is closest to the IC50; therefore, we suggest that the initial testing of candidate drugs for repurposing could select the AUC pharmacokinetic parameter and not the Cmax as the translated drug concentration for in vitro testing. Nevertheless, this is a suggestion only as experimental evidence does not exist to prove this concept. Studies on this issue are required to advance in cancer drug repurposing.

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Acknowledgements

BARB gratefully acknowledges Consejo Nacional de Ciencia y Tecnología (CONACyT) for his Ph.D. scholarship.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Author notes

  1. Benjamin Robles-Bañuelos and Adriana Romo-Perez have contributed equally to this work.

Authors and Affiliations

  1. Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico

    Benjamin Robles-Bañuelos & Alfonso Duenas-Gonzalez

  2. Instituto de Química, Universidad Nacional Autónoma de México, Mexico City, Mexico

    Adriana Romo-Perez

  3. Subdirección de Investigación Básica, Instituto Nacional de Cancerología, San Fernando 22, Belisario Domínguez Secc 16, Tlalpan, 14080, Mexico City, Mexico

    Guadalupe Dominguez-Gomez, Alma Chavez-Blanco, Aurora Gonzalez-Fierro & Alfonso Duenas-Gonzalez

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  1. Benjamin Robles-Bañuelos
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  4. Alma Chavez-Blanco
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  6. Alfonso Duenas-Gonzalez
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Contributions

All authors have contributed to the study conception and design. Material preparation was performed by ARP, BRB, and ADG. Data collection was performed by ADG, BRB, GDG, ACB, ARP, and AGF. Analysis was performed by BRB, ARP, and A.D.G. The first draft of the manuscript was written by A.D.G. and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Alfonso Duenas-Gonzalez.

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Robles-Bañuelos, B., Romo-Perez, A., Dominguez-Gomez, G. et al. Selection of clinically relevant drug concentrations for in vitro studies of candidates drugs for cancer repurposing: a proposal. Clin Transl Oncol 26, 1077–1088 (2024). https://doi.org/10.1007/s12094-023-03352-w

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