RESUMO
More than 20% of metastatic prostate cancer carries genomic defects involving DNA damage repair pathways, mainly in homologous recombination repair-related genes. The recent approval of olaparib has paved the way to precision medicine for the treatment of metastatic prostate cancer with PARP inhibitors in this subset of patients, especially in the case of BRCA1 or BRCA2 pathogenic/likely pathogenic variants. In face of this new therapeutic opportunity, many issues remain unsolved. This narrative review aims to describe the relationship between homologous recombination repair deficiency and prostate cancer, the techniques used to determine homologous recombination repair status in prostate cancer, the crosstalk between homologous recombination repair and the androgen receptor pathway, the current evidence on PARP inhibitors activity in metastatic prostate cancer also in homologous recombination repair-proficient tumors, as well as emerging mechanisms of resistance to PARP inhibitors. The possibility of combination therapies including a PARP inhibitor is an attractive option, and more robust data are awaited from ongoing phase II and phase III trials outlined in this manuscript.
Assuntos
Inibidores de Poli(ADP-Ribose) Polimerases , Neoplasias da Próstata , Reparo de DNA por Recombinação , Humanos , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Proteína BRCA2/genética , Proteína BRCA2/deficiência , Metástase Neoplásica , Proteína BRCA1/genética , Proteína BRCA1/deficiência , Ftalazinas/uso terapêutico , Ftalazinas/farmacologia , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , PiperazinasAssuntos
Biomarcadores Tumorais/metabolismo , Proliferação de Células , Fatores Reguladores de Interferon/genética , Leucemia Linfocítica Crônica de Células B/patologia , Mutação , Proteínas Proto-Oncogênicas c-myc/metabolismo , Idoso , Biomarcadores Tumorais/genética , Estudos de Coortes , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Fatores Reguladores de Interferon/metabolismo , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/metabolismo , Masculino , Prognóstico , Proteínas Proto-Oncogênicas c-myc/genética , Células Tumorais CultivadasRESUMO
Introduction: Vaginal cancer is a rare gynecologic malignancy. While in a localized disease, concurrent chemoradiation grants local control and better overall survival, in a metastatic setting, the management options are very limited. Furthermore, recurrent cervical, vulvar, and vaginal carcinomas notoriously develop resistance to treatment, and consequently, their prognosis is still poor. Case Presentation: We herein present the case of a woman with a nodal relapse of vaginal carcinoma, effectively treated with third-line immunotherapy. We will also provide a review of the literature on the new therapeutic strategies for advanced vaginal carcinoma, with a focus on pembrolizumab immunotherapy. Conclusion: Pembrolizumab might represent a promising option for the management of vaginal and vulvar cancer, but data to support its use in this setting are still lacking. This case highlights the need for further investigation and trial designs for this rare disease.