The International Journal of Developmental Biology

Int. J. Dev. Biol. 57: 273 - 280 (2013)

Vol 57, Issue 2-3-4

Special Issue: Male Germ Cells in Development & Tumors

Revisiting DNA damage repair, p53-mediated apoptosis and cisplatin sensitivity in germ cell tumors

Published: 30 May 2013

Francesca Cavallo1,2, Darren R. Feldman3 and Marco Barchi*,1

1Department of Biomedicine and Prevention, University of Rome Tor Vergata, Italy, 2Developmental Biology Program, 3Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA


Testicular germ cell tumors (TGCTs), ie, seminomas and nonseminomas, account for 1% to 3% of all neoplasms in men. They are the most common cancer in young white males and are unique in their responsiveness to cisplatin-based chemotherapy. For this reason, TGCTs are considered a model for curative disease. However, up to now, the molecular mechanisms behind this exceptional responsiveness to DNA-damaging agents have remained unclear. A hypersensitive apoptotic response, as well as a reduction in the proficiency to repair cisplatin-induced DNA damage might account for this behavior. In this review, building on recent findings of p53-induced apoptosis and DNA-repair mechanisms in TGCTs, we will discuss the molecular bases that drive tumor sensitivity to cisplatin, emphasizing the new therapeutic approaches proposed to eventually constrain tumor recurrence, and target TGCTs which are unresponsive to standard therapies.


p53, XPF, ERCC1, homologous recombination (HR), nutlin-3, MDM2

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