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REVIEW article

Front. Genet.
Sec. Cancer Genetics and Oncogenomics
Volume 15 - 2024 | doi: 10.3389/fgene.2024.1480417
This article is part of the Research Topic Recent advances in Genomics and Oncogenomics for Personalized Medicine View all 5 articles

PARP inhibitors in testicular germ cell tumors: what we know and what we are looking for

Provisionally accepted
Sara Parola Sara Parola 1Christoph Oing Christoph Oing 2Pasquale Rescigno Pasquale Rescigno 2Salvatore Feliciano Salvatore Feliciano 1Francesca Carlino Francesca Carlino 1Luca Pompella Luca Pompella 1Antonella Lucia Marretta Antonella Lucia Marretta 1Irene De Santo Irene De Santo 1Martina Viggiani Martina Viggiani 3Margherita Muratore Margherita Muratore 4Bianca Arianna Facchini Bianca Arianna Facchini 5Jessica Orefice Jessica Orefice 5Eleonora Cioli Eleonora Cioli 5Francesca Sparano Francesca Sparano 6Domenico Mallardo Domenico Mallardo 6Ugo De Giorgi Ugo De Giorgi 7Giovannella Palmieri Giovannella Palmieri 8Paolo Antonio Ascierto Paolo Antonio Ascierto 6Margaret Ottaviano Margaret Ottaviano 6*
  • 1 Medical Oncology Unit, Ospedale Ave Gratia Plena, ASL Caserta, San Felice a Cancello, Italy
  • 2 Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, England, United Kingdom
  • 3 Medical Oncology Unit, Ospedale San Giuseppe Moscati, ASL Caserta, Aversa, Italy
  • 4 Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy
  • 5 Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples, Campania, Italy
  • 6 Unit of Melanoma, Cancer Immunotherapy and Development Therapeutics, G. Pascale National Cancer Institute Foundation (IRCCS), Naples, Campania, Italy
  • 7 Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy
  • 8 Rare Tumors Coordinating Center of Campania Region (CRCTR), Naples, Italy

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

    Testicular germ cell tumors (TGCTs), the most common malignancies affecting young men, are characterized by high sensitivity to cisplatin-based chemotherapy, which leads to high cure rates even in metastatic disease. However, approximately 30% of patients with metastatic TGCTs relapse after first-line treatment and those who can be defined as platinum-refractory patients face a very dismal prognosis with only limited chemotherapy-based treatment options and an overall survival of few months. Hence, to understand the mechanisms underlying cisplatin resistance is crucial for developing new treatment strategies. This narrative review explores the potential role of PARP inhibitors (PARPis) in overcoming cisplatin resistance in TGCTs, starting from the rationale of their ability to induce DNA damage in cells with homologous recombination repair (HRR). Thus far, PARPis have failed to show meaningful clinical activity in platinum-refractory TGCT patients, either alone or in combination with chemotherapy. However, few responses to PARPis in TGCTs have been detected in patients with BRCA1/2, ATM or CHEK2 mutations, reinforcing the idea that patients should be optimally selected for tailored treatments in the era of personalized medicine. Future preclinical and clinical research is needed to further investigate the molecular mechanisms of cisplatin resistance and to identify novel therapeutic strategies in resistant/refractory TGCTs patients.

    Keywords: testicular tumors, germ cell tumors, cisplatin resistance, PARP inhibitors, DNA damage response, homologous recombination repair

    Received: 13 Aug 2024; Accepted: 12 Nov 2024.

    Copyright: © 2024 Parola, Oing, Rescigno, Feliciano, Carlino, Pompella, Marretta, De Santo, Viggiani, Muratore, Facchini, Orefice, Cioli, Sparano, Mallardo, De Giorgi, Palmieri, Ascierto and Ottaviano. 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: Margaret Ottaviano, Unit of Melanoma, Cancer Immunotherapy and Development Therapeutics, G. Pascale National Cancer Institute Foundation (IRCCS), Naples, 80131, Campania, Italy

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.