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

Autor:	Parola S; Medical Oncology Unit, Ospedale Ave Gratia Plena, ASL Caserta, San Felice a Cancello, Italy., Oing C; Translational and Clinical Research Institute, Centre for Cancer, Newcastle University, Newcastle Upon Tyne, United Kingdom., Rescigno P; Translational and Clinical Research Institute, Centre for Cancer, Newcastle University, Newcastle Upon Tyne, United Kingdom., Feliciano S; Medical Oncology Unit, Ospedale Ave Gratia Plena, ASL Caserta, San Felice a Cancello, Italy., Carlino F; Medical Oncology Unit, Ospedale Ave Gratia Plena, ASL Caserta, San Felice a Cancello, Italy., Pompella L; Medical Oncology Unit, Ospedale Ave Gratia Plena, ASL Caserta, San Felice a Cancello, Italy., Marretta AL; Medical Oncology Unit, Ospedale Ave Gratia Plena, ASL Caserta, San Felice a Cancello, Italy., De Santo I; Medical Oncology Unit, Ospedale Ave Gratia Plena, ASL Caserta, San Felice a Cancello, Italy., Viggiani M; Medical Oncology Unit, Ospedale San Giuseppe Moscati, ASL Caserta, Aversa, Italy., Muratore M; Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy., Facchini BA; Department of Precision Medicine, Università degli Studi della Campania 'Luigi Vanvitelli', Naples, Italy., Orefice J; Department of Precision Medicine, Università degli Studi della Campania 'Luigi Vanvitelli', Naples, Italy., Cioli E; Department of Precision Medicine, Università degli Studi della Campania 'Luigi Vanvitelli', Naples, Italy., Sparano F; Department of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, Italy., Mallardo D; Department of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, Italy., De Giorgi U; Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy., Palmieri G; Rare Tumors Coordinating Center of Campania Region (CRCTR), Naples, Italy., Ascierto PA; Department of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, Italy., Ottaviano M; Department of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, Italy.
Jazyk:	angličtina
Zdroj:	Frontiers in genetics [Front Genet] 2024 Nov 29; Vol. 15, pp. 1480417. Date of Electronic Publication: 2024 Nov 29 (Print Publication: 2024).
DOI:	10.3389/fgene.2024.1480417
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. (Copyright © 2024 Parola, Oing, Rescigno, Feliciano, Carlino, Pompella, Marretta, De Santo, Viggiani, Muratore, Facchini, Orefice, Cioli, Sparano, Mallardo, De Giorgi, Palmieri, Ascierto and Ottaviano.)
Databáze:	MEDLINE
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