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Anticancer Drugs ; 26(2): 224-6, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25304989

RESUMO

Patients with BRCA-1 and BRCA-2 germ line mutations are at an increased risk of developing pancreatic adenocarcinoma (PAC). In particular, the BRCA-2 mutation has been associated with a relative risk of developing PAC of 3.51. The BRCA-2 protein is involved in repair of double-stranded DNA breaks. Recent reports have suggested that in the setting of impaired DNA repair, chemotherapeutic agents that induce DNA damage, such as platinum-based antineoplastic drugs (platins) and poly(ADP-ribose) polymerase inhibitors (PARP inhibitors), have improved efficacy. However, because of the relative rarity of BRCA-related PAC, studies evaluating such agents in this setting are scarce. Patients with a known BRCA-2 mutation and PAC were retrospectively reviewed. Ten patients with PAC and BRCA-2 mutation were identified. Four patients (40%) were of Ashkenazi Jewish descent. Seven patients (70%) received platinum agents, two (20%) received mitomycin-C, one (10%) received a PARP inhibitor, and seven (70%) received a topoisomerase-I inhibitor. Overall, chemotherapy was well tolerated with expected side effects. Patients with a BRCA-2 mutation and PAC represent a group with a unique biology underlying their cancer. Chemotherapies such as platinum derivatives, mitomycin-C, topoisomerase-I inhibitors, and PARP inhibitors targeting DNA require further investigation in this population. Genetic testing may guide therapy in the future.


Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Antineoplásicos/uso terapêutico , Proteína BRCA2/genética , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Judeus/genética , Masculino , Pessoa de Meia-Idade , Mitomicina/uso terapêutico , Compostos Organoplatínicos/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases , Estudos Retrospectivos , Inibidores da Topoisomerase I/uso terapêutico , Resultado do Tratamento
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