TY - JOUR
T1 - PARP inhibitors in endometrial cancer
T2 - Current status and perspectives
AU - Musacchio, Lucia
AU - Caruso, Giuseppe
AU - Pisano, Carmela
AU - Cecere, Sabrina Chiara
AU - Di Napoli, Marilena
AU - Attademo, Laura
AU - Tambaro, Rosa
AU - Russo, Daniela
AU - Califano, Daniela
AU - Palaia, Innocenza
AU - Muzii, Ludovico
AU - Panici, Pierluigi Benedetti
AU - Pignata, Sandro
PY - 2020
Y1 - 2020
N2 - Advanced, recurrent and metastatic endometrial cancer (EC) has a dismal prognosis due to poor response rates to conventional treatments. In the era of precision medicine, the improved understanding of cancer genetics and molecular biology has led to the development of targeted therapies, such as poly (ADP-ribose) polymerase (PARP) inhibitors. This class of drugs that inhibit PARP enzymes has been investigated in many different types of tumors and its use in the treatment of gynecological malignancies has rapidly increased over the past few years. Data from several clinical trials showed that PARP inhibitors have a beneficial role in cancers with a defect in the homologous DNA recombination system, regardless of the BRCA mutational status. Since EC frequently shows mutations in PTEN and TP53 genes, indirectly involved in the homologous DNA recombination pathway, several in vivo and in vitro studies investigated the efficacy of PARP inhibitors in EC, showing promising results. This review will discuss the use of PARP inhibitors in endome-trial cancer, summarizing data from preclinical studies and providing an overview of the ongoing trials, with a special focus on the development of combined treatment strategies with PARP inhibitors and immune checkpoint inhibitors.
AB - Advanced, recurrent and metastatic endometrial cancer (EC) has a dismal prognosis due to poor response rates to conventional treatments. In the era of precision medicine, the improved understanding of cancer genetics and molecular biology has led to the development of targeted therapies, such as poly (ADP-ribose) polymerase (PARP) inhibitors. This class of drugs that inhibit PARP enzymes has been investigated in many different types of tumors and its use in the treatment of gynecological malignancies has rapidly increased over the past few years. Data from several clinical trials showed that PARP inhibitors have a beneficial role in cancers with a defect in the homologous DNA recombination system, regardless of the BRCA mutational status. Since EC frequently shows mutations in PTEN and TP53 genes, indirectly involved in the homologous DNA recombination pathway, several in vivo and in vitro studies investigated the efficacy of PARP inhibitors in EC, showing promising results. This review will discuss the use of PARP inhibitors in endome-trial cancer, summarizing data from preclinical studies and providing an overview of the ongoing trials, with a special focus on the development of combined treatment strategies with PARP inhibitors and immune checkpoint inhibitors.
KW - Endometrial cancer
KW - Homologous recombination deficiency
KW - Immune checkpoint inhibitors
KW - P53 mutation
KW - PARP inhibitors
KW - PTEN mutation
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U2 - 10.2147/CMAR.S221001
DO - 10.2147/CMAR.S221001
M3 - Review article
AN - SCOPUS:85088242478
VL - 12
SP - 6123
EP - 6135
JO - Cancer Management and Research
JF - Cancer Management and Research
SN - 1179-1322
ER -