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BRIEF RESEARCH REPORT article

Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1444973
This article is part of the Research Topic Ovarian Cancer Targeted Medication: PARP Inhibitors, Anti-Angiogenic Drugs, Immunotherapy, and More – Volume II View all 17 articles

The first-in-class proapoptotic peptide PEP-010 is effective in monotherapy and in combination with Paclitaxel on resistant ovarian adenocarcinoma cell models

Provisionally accepted
Aline Lacroix Aline Lacroix 1Rayan Farhat Rayan Farhat 1Aude Robert Aude Robert 2Catherine Brenner Catherine Brenner 3Joëlle Wiels Joëlle Wiels 3Diego Germini Diego Germini 1*
  • 1 PEP-Therapy, Paris, France
  • 2 UMR1279 INSERM, Gustave Roussy, Villejuif, France
  • 3 Gustave Roussy, Université Paris-Saclay, UMR9018 Metabolic and Systemic Aspects of Oncogenesis (METSY), Villejuif, Île-de-France, France

The final, formatted version of the article will be published soon.

    Ovarian adenocarcinoma is the gynecological malignancy with the worst prognosis and the highest mortality rate. In the first stages of treatment, chemotherapy results effective, but its prolonged use and high doses lead to the appearance of resistance to treatments and relapse in most patients, representing a major challenge for clinicians. We developed PEP-010, a cell-penetrating proapoptotic peptide disrupting the protein-protein interaction between caspase-9 and protein phosphatase 2A, thereby leading to the recovery of their activity in the apoptotic pathway. We show here that PEP-010 effectively induces cell death in monotherapy in up to 55% of cells from ovarian adenocarcinoma cell models resistant to different chemotherapies. Moreover, when used in combination with paclitaxel, one of the therapeutic options for recurrent ovarian carcinoma, PEP-010 showed a beneficial effect leading to the reduction of the IC50 of paclitaxel of 2.2 times and to apoptosis in 87% of cells. The described results suggest the potential therapeutic interest for PEP-010 and lead to the choice of ovarian adenocarcinoma as one of the major indications of the ongoing clinical trial.

    Keywords: Apoptosis, peptide, Monotherapy, combination therapy, Ovarian adenocarcinoma

    Received: 06 Jun 2024; Accepted: 11 Jul 2024.

    Copyright: © 2024 Lacroix, Farhat, Robert, Brenner, Wiels and Germini. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Diego Germini, PEP-Therapy, Paris, France

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