Communications
29 September 2021
Vol. 2 No. 1 (2021)
https://doi.org/10.4081/bse.164

Targeting cancer drug resistance by modulation of ERCC1-XPF and p53 activity

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Drug resistance, ERCC1-XPF, p53, cancer therapy
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Authors

Gloria Ciniero
gloria.ciniero@polito.it
PolitoBIOMedLab, Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Torino, Italy.
Francesco Gentile
University of Alberta, Faculty of Medicine & Dentistry, Edmonton, AB, Canada.
Ahmed H. Elmenoufy
University of Alberta, Faculty of Medicine & Dentistry, Edmonton, AB, Canada.
Emeline Cros-Perrial
Université Claude Bernard Lyon 1, Lyon, France.
Frederick G. West
University of Alberta, Faculty of Medicine & Dentistry, Edmonton, AB, Canada.
Michael Weinfeld
University of Alberta, Faculty of Medicine & Dentistry, Edmonton, AB, Canada.
Marco A. Deriu
PolitoBIOMedLab, Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Torino, Italy.
Lars P. Jordheim
Université Claude Bernard Lyon 1, Lyon, France.
Jack A. Tuszynski
PolitoBIOMedLab, Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Torino, Italy.

New disruptors of the ERCC1-XPF interaction interaction have a synergistic effect with traditional NER inhibitors, in p53 positive cells. Furthermore, the synergy can be resumed in p53 negative cells upon reactivation of the TP53 gene.

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[1] Gentile, F, Elmenoufy, AH, Ciniero, G, et al. Computer-aided drug design of small molecule inhibitors of the ERCC1-XPF protein–protein interaction. Chem Biol Drug Des 2020;95:460– 71.
[2] Jordheim LP, Barakat KH, Heinrich-Balard L, et al. Small molecule inhibitors of ERCC1-XPF protein-protein interaction synergize alkylating agents in cancer cells. Mol Pharmacol 2013;84:12-24.
[3] Friboulet L, Soria JC, Olaussen KA. The “Guardian of the Genome”—An Old Key to Unlock the ERCC1 Issue. Clin Cancer Res 2019;25:2369-71.
[4] Ciniero G, Elmenoufy AH, Gentile F, et al. Enhancing the activity of platinum-based drugs by improved inhibitors of ERCC1-XPF-mediated DNA repair. Cancer Chemother Pharmacol 2021;87:259-67.

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Targeting cancer drug resistance by modulation of ERCC1-XPF and p53 activity. (2021). Biomedical Science and Engineering, 2(1). https://doi.org/10.4081/bse.164

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