Inhibiteurs de PARP et radiothérapie : rationnel et perspectives pour une utilisation en clinique

Pernin, Vincent; Mégnin-Chanet, Frédérique; Pennaneach, Vincent; Kirova, Y.; Hall, Jesse

doi:10.1016/j.canrad.2014.09.001

Cited by 1 publication

(2 citation statements)

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“…Normal cells have the ability to repair this damage by a protection mechanism maintaining its normal function, but the tumor cells' ability to repair DNA is a radio-resistance mechanism. In recent years, studies have identified a number of agents in these pathways such as PARP inhibitors [43].…”

Section: Inhibitors Of Poly (Adp -Ribose) Polymerasementioning

confidence: 99%

“…Data suggest that PARP inhibitors may enhance the effects of radiation in various types of tumors, such as lung cancer, colorectal, and cervical among others [67]. However, the mechanism of action is still unknown, one hypothesis is that it is due to mutual damage (of PARP-inhibitors and radiotherapy) of DNA or whether tumor re-oxygenation contributes to this radio sensitization via the vasoactive effects of the PARP inhibitors remains to be fully determined [43].…”

Section: Combination Therapy Of Parp Inhibitors and Radiotherapymentioning

confidence: 99%

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Individualized Novel Therapies for Patients with Tumor Suppressor Genes BRCA1 and BRCA2 Mutated Epithelial Ovarian Cancer

Garcia-Nieto¹,

Guillén‐Ponce²,

Alonso³

et al. 2016

Gynecologic Cancers - Basic Sciences, Clinical and Therapeutic Perspectives

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Ovarian cancer is the leading cause of death in women with gynecological cancer, since a large proportion of patients are diagnosed at later stages of the disease. The incidence of ovarian cancer in the general population is %, but patients with germline mutations in the BRCA genes have a risk of developing ovarian cancer of up to % with a cumulative risk of ovarian cancer at years of age of % in BRCA and % in BRCA mutation carriers. Although it is a chemosensitive tumor, most of the patients after surgery and chemotherapy based on taxanes and platinum will relapse later in life. Due to the high risk of developing ovarian cancer in patients with BRCA germline mutations, new treatments rely increasingly on histological and molecular characteristics of the primary tumor, achieving greater selectivity and lower toxicity compared with standard cytotoxic agents. Poly ADP-ribose polymerase PARPS inhibitors are the first biologically active agents for patients with ovarian cancer with alterations in the DNA repair pathway, particularly in the high-grade serous subtype of ovarian cancer.The results of clinical trials published so far mean that olaparib has been approved, pending the results of the Phase III trials. The European Medicines Agency EMA adopted olaparib lynparza ® on the December , , as a maintenance therapy after response to platinum-based chemotherapy in relapsed platinum-sensitive ovarian cancer patients with a BRCA mutation. By contrast, the Food and Drug Administration FDA approved olaparib on December , , in patients with high-grade ovarian epithelial serous tumors and a BRCA mutation who have progressed during three or more lines of chemotherapy. Olaparib is also used in primary fallopian tube and peritoneal cancers with BRCA mutations.

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Section: Inhibitors Of Poly (Adp -Ribose) Polymerasementioning

confidence: 99%

Section: Combination Therapy Of Parp Inhibitors and Radiotherapymentioning

confidence: 99%