التفاصيل البيبلوغرافية
| العنوان: |
PARP inhibitors in platinum-sensitive high-grade serous ovarian cancer. |
| المؤلفون: |
Morgan, Robert D., Clamp, Andrew R., Evans, D. Gareth R., Edmondson, Richard J., Jayson, Gordon C. |
| المصدر: |
Cancer Chemotherapy & Pharmacology; Apr2018, Vol. 81 Issue 4, p647-658, 12p |
| مصطلحات موضوعية: |
OVARIAN cancer treatment, POLY(ADP-ribose) polymerase, CANCER chemotherapy, DRUG resistance, CLINICAL trials, DRUG resistance in cancer cells, OVARIAN tumors, PLATINUM, TUMORS |
| مستخلص: |
Purpose: Poly(ADP-ribose) polymerase inhibitors (PARPi) have changed the management of high-grade serous ovarian cancer (HGSOC). The rationale for the development of PARPi was based on the concept of synthetic lethality, in which a cell can survive a deficiency of one gene/gene product, but may die if there is a deficiency in a combination of genes/gene products. In women with BRCA1/2 deficiency within their ovarian cancer tissue, inhibition of PARP imposes an intolerable burden of DNA damage repair deficiency and may induce cell death.Methods: Clinical trials have evaluated PARPi as single-agent therapeutics and as maintenance treatment following platinum-based chemotherapy for HGSOC. Clinical data suggest the most impressive anti-tumour activity occurs in women with platinum-sensitive ovarian cancer and germline or somatic BRCA1/2 mutations (g/sBRCAmt).Results: In the maintenance setting, randomised trials have shown that PARPi compared to placebo reduce the hazard ratio for the development of progressive disease to 0.2-0.27 for patients with a g/sBRCAmt; to 0.34-0.38 for patients with putative evidence of DNA damage repair deficiency; and to 0.35-0.45 in an unselected population with HGSOC. Furthermore, phase 1/2 trials have reported single-agent anti-tumour response rates in gBRCAmt of approximately 50% in platinum-sensitive and 25% in platinum-resistant disease.Conclusion: Here, we discuss the evidence for the use of PARPi as single-agent therapeutics and maintenance treatment in HGSOC and evaluate the genetic assays used in clinical trials so far. We discuss the emerging role of platinum sensitivity as a broad eligibility criteria for the use of PARPi. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
