PARP Inhibitors in Endometrial Cancer: Current Status and Perspectives

PARP Inhibitors in Endometrial Cancer: Current Status and Perspectives

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 pol...

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Bibliographic Details
Published in:Cancer management and research 2020-07, Vol.12, p.6123-6135
Main Authors: Musacchio, Lucia, Caruso, Giuseppe, Pisano, Carmela, Cecere, Sabrina Chiara, Di Napoli, Marilena, Attademo, Laura, Tambaro, Rosa, Russo, Daniela, Califano, Daniela, Palaia, Innocenza, Muzii, Ludovico, Panici, Pierluigi Benedetti, Pignata, Sandro
Format: Article
Language:eng
Subjects:
Cancer
Cancer genetics
Cancer research
Care and treatment
Development and progression
Endometrial cancer
Genes
homologous recombination deficiency
immune checkpoint inhibitors
Ionizing radiation
Molecular biology
Monosaccharides
p53 mutation
parp inhibitors
Precision medicine
Prognosis
pten mutation
Review
Tumor proteins
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Summary: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 endometrial 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. Keywords: endometrial cancer, PARP inhibitors, PTEN mutation, P53 mutation, homologous recombination deficiency, immune checkpoint inhibitors
ISSN:1179-1322
1179-1322