Advanced ovarian cancer is a catastrophic disease and a leading cause of cancer-associated mortality in US women as it presents late and has a high recurrence rate. In 2014 bevacizumab and olaparib were approved by the Food and Drug Administration, the first new drugs since 2006. Olaparib (Lynparza) is the first-in-class polyadenosine 5'-diphosphoribose polymerase (PARP) inhibitor for recurrent ovarian cancer in women with gBRCAmut. This chapter reviews the translational science behind the development of PARP inhibitors and the opportunities and inherent limitations of therapy targeting tumors with homologous recombination deficiency (HRD). After the proven benefit of this drug in BRCA-mutated patients, the molecular understanding of ovarian cancer may lead to a broader exploitation of this treatment approach. Promising clinical data suggests a role in DNA scarred high-grade serous ovarian cancer, ataxia telangiectasia mutated (ATM) low-expressing gastric cancer, and prostate cancer with disrupted DNA-repair genes. The very mutations that increase the cancer risk in patients are now seen as the key to fighting their disease and other tumors with HRD.
Collins, B., Gonzalez, A., Hanbury, A., Ceppi, L., Penson, R. (2017). Molecular Basis of PARP Inhibition and Future Opportunities in Ovarian Cancer Therapy. In Translational Advances in Gynecologic Cancers (pp. 129-150). Elsevier Inc. [10.1016/B978-0-12-803741-6.00007-0].
Molecular Basis of PARP Inhibition and Future Opportunities in Ovarian Cancer Therapy
Ceppi L.Membro del Collaboration Group
;
2017
Abstract
Advanced ovarian cancer is a catastrophic disease and a leading cause of cancer-associated mortality in US women as it presents late and has a high recurrence rate. In 2014 bevacizumab and olaparib were approved by the Food and Drug Administration, the first new drugs since 2006. Olaparib (Lynparza) is the first-in-class polyadenosine 5'-diphosphoribose polymerase (PARP) inhibitor for recurrent ovarian cancer in women with gBRCAmut. This chapter reviews the translational science behind the development of PARP inhibitors and the opportunities and inherent limitations of therapy targeting tumors with homologous recombination deficiency (HRD). After the proven benefit of this drug in BRCA-mutated patients, the molecular understanding of ovarian cancer may lead to a broader exploitation of this treatment approach. Promising clinical data suggests a role in DNA scarred high-grade serous ovarian cancer, ataxia telangiectasia mutated (ATM) low-expressing gastric cancer, and prostate cancer with disrupted DNA-repair genes. The very mutations that increase the cancer risk in patients are now seen as the key to fighting their disease and other tumors with HRD.
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