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


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


[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.
Ciniero, G., Gentile, F., Elmenoufy, A. H., Cros-Perrial, E. ., West, F. G., Weinfeld, M., Deriu, M. A., Jordheim, L. P., & Tuszynski, J. A. (2021). Targeting cancer drug resistance by modulation of ERCC1-XPF and p53 activity. Biomedical Science and Engineering, 2(1). https://doi.org/10.4081/bse.164

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