Franco Muggia, MD
PARP enzymes are involved in a number of DNA repair processes. Tumors with pathogenic BRCA
mutations are associated with a deficiency in homologous recombination, a critical double-stranded DNA repair process. When patients with these tumors are treated with PARP inhibitors, the combination of DNA repair deficiencies may lead to tumor toxicity while sparing noncancerous tissue that has relatively intact BRCA function. Exploiting selective cellular susceptibilities by affecting parallel pathways has been called synthetic lethality. Applications of this concept in women’s cancers emerged more than a decade ago in the context of the vulnerabilities of BRCA1
null ovarian cancer cells when exposed to PARP inhibitors. Since this first positive signal, these drugs have eventually undergone numerous trials obtaining specific indications as monotherapy. More recently, they have sought to be integrated within emerging therapeutic strategies in not only ovarian cancer but also breast cancer.
PARP Inhibition in Ovarian Cancer
After years in development, several PARP inhibitors have achieved indications in ovarian cancer treatment, while others continue in development and expanding indications (Table 1
). The approved roles of PARP inhibitors in ovarian cancer fall into 2 main approaches: treatment of recurrent disease and maintenance after response to platinum-based chemotherapy.
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