Role of DNA repair machinery and p53 in the testicular germ cell cancer: a review

Francesco Jacopo Romano, Sabrina Rossetti, Carla Cavaliere, Rossella Di Franco, Elvira La Mantia, Luigi Castaldo, Flavia Nocerino, Gianluca Ametrano, Francesca Cappuccio, Maria Gabriella Malzone, Micaela Montanari, Daniela Vanacore, Vincenzo Quagliariello, Raffaele Piscitelli, Maria Filomena Pepe, Carmine D'Aniello, Sisto Perdonà, Paolo Muto, Gerardo Botti, Gennaro CilibertoBianca Maria Veneziani, Francesco De Falco, Piera Maiolino, Michele Caraglia, Maurizio Montella, Gaetano Facchini

Research output: Contribution to journalArticle

Abstract

Notwithstanding the peculiar sensitivity to cisplatin-based treatment, resulting in a very high percentage of cures even in advanced stages of the disease, still we do not know the biological mechanisms that make Testicular Germ Cell Tumor (TGCT) "unique" in the oncology scene. p53 and MDM2 seem to play a pivotal role, according to several in vitro observations, but no correlation has been found between their mutational or expression status in tissue samples and patients clinical outcome. Furthermore, other players seem to be on stage: DNA Damage Repair Machinery (DDR) , especially Homologous Recombination (HR) proteins, above all Ataxia Telangiectasia Mutated (ATM), cooperates with p53 in response to DNA damage, activating apoptotic cascade and contributing to cell "fate". Homologous Recombination deficiency has been assumed to be a Germ Cell Tumor characteristic underlying platinum-sensitivity, whereby Poly(ADP-ribose) polymerase (PARP), an enzyme involved in HR DNA repair, is an intriguing target: PARP inhibitors have already entered in clinical practice of other malignancies and trials are recruiting TGCT patients in order to validate their role in this disease. This paper aims to summarize evidence, trying to outline an overview of DDR implications not only in TGCT curability, but also in resistance to chemotherapy.

Original languageEnglish
Pages (from-to)85641-85649
Number of pages9
JournalOncotarget
Volume7
Issue number51
DOIs
Publication statusPublished - Dec 20 2016

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Keywords

  • Review
  • Journal Article

Cite this

Romano, F. J., Rossetti, S., Cavaliere, C., Di Franco, R., La Mantia, E., Castaldo, L., Nocerino, F., Ametrano, G., Cappuccio, F., Malzone, M. G., Montanari, M., Vanacore, D., Quagliariello, V., Piscitelli, R., Pepe, M. F., D'Aniello, C., Perdonà, S., Muto, P., Botti, G., ... Facchini, G. (2016). Role of DNA repair machinery and p53 in the testicular germ cell cancer: a review. Oncotarget, 7(51), 85641-85649. https://doi.org/10.18632/oncotarget.13063