TY - JOUR
T1 - Role of DNA repair machinery and p53 in the testicular germ cell cancer
T2 - A review
AU - Romano, Francesco Jacopo
AU - Rossetti, Sabrina
AU - Conteduca, Vincenza
AU - Schepisi, Giuseppe
AU - Cavaliere, Carla
AU - Di Franco, Rossella
AU - La Mantia, Elvira
AU - Castaldo, Luigi
AU - Nocerino, Flavia
AU - Ametrano, Gianluca
AU - Cappuccio, Francesca
AU - Malzone, Gabriella
AU - Montanari, Micaela
AU - Vanacore, Daniela
AU - Quagliariello, Vincenzo
AU - Piscitelli, Raffaele
AU - Pepe, Maria Filomena
AU - Berretta, Massimiliano
AU - D'Aniello, Carmine
AU - Perdonà, Sisto
AU - Muto, Paolo
AU - Botti, Gerardo
AU - Ciliberto, Gennaro
AU - Veneziani, Bianca Maria
AU - De Falco, Francesco
AU - Maiolino, Piera
AU - Caraglia, Michele
AU - Montella, Maurizio
AU - De Giorgi, Ugo
AU - Facchini, Gaetano
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - ATM
KW - DDR
KW - Germ cell cancer
KW - P53
KW - Testis
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U2 - 10.18632/oncotarget.13063
DO - 10.18632/oncotarget.13063
M3 - Review article
AN - SCOPUS:85007478185
VL - 7
SP - 85641
EP - 85649
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 51
ER -