RESUMEN
The standard of care for advanced or metastatic urothelial carcinoma (mUC) was historically identified with platinum-based chemotherapy. Thanks to the advances in biological and genetic knowledge and technologies, new therapeutic agents have emerged in this setting recently: the immune checkpoint inhibitors and the fibroblast growth factor receptor inhibitors as the target therapy for patients harboring alterations in the fibroblast growth factor receptor (FGFR) pathway. However, chasing a tumor's tendency to recur and progress, a new class of agents has more recently entered the scene, with promising results. Antibody-drug conjugates (ADCs) are in fact the latest addition, with enfortumab vedotin being the first to receive accelerated approval by the U.S. Food and Drug Administration in December 2019, followed by sacituzumab govitecan. Many other ADCs are still under investigation. ADCs undoubtedly represent the new frontier, with the potential of transforming the management of mUC treatment in the future. Therefore, we reviewed the landscape of mUC treatment options, giving an insight into the molecular basis and mechanisms, and evaluating new therapeutic strategies in the perspective of more and more personalized treatments.
Asunto(s)
Inmunoconjugados , Humanos , Inmunoconjugados/uso terapéutico , Metástasis de la Neoplasia , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Urológicas/tratamiento farmacológico , Neoplasias Urológicas/patología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Terapia Molecular Dirigida/métodos , Receptores de Factores de Crecimiento de Fibroblastos/antagonistas & inhibidores , Receptores de Factores de Crecimiento de Fibroblastos/metabolismo , Anticuerpos Monoclonales/uso terapéutico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/metabolismo , Camptotecina/análogos & derivadosRESUMEN
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.
Asunto(s)
Inhibidores de Poli(ADP-Ribosa) Polimerasas , Neoplasias de la Próstata , Reparación del ADN por Recombinación , Humanos , Masculino , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Proteína BRCA2/genética , Proteína BRCA2/deficiencia , Metástasis de la Neoplasia , Proteína BRCA1/genética , Proteína BRCA1/deficiencia , Ftalazinas/uso terapéutico , Ftalazinas/farmacología , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , PiperazinasAsunto(s)
Carcinoma Hepatocelular , Clorpromazina , Hipnóticos y Sedantes , Neoplasias Hepáticas , Trasplante de Hígado , Midazolam , Cuidados Paliativos , Humanos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/tratamiento farmacológico , Midazolam/administración & dosificación , Midazolam/uso terapéutico , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/tratamiento farmacológico , Clorpromazina/uso terapéutico , Clorpromazina/administración & dosificación , Hipnóticos y Sedantes/administración & dosificación , Hipnóticos y Sedantes/uso terapéutico , Masculino , Persona de Mediana EdadRESUMEN
The severe acute respiratory syndrome, coronavirus 2 (SARS-CoV-2), is a positive-sense single-stranded ribonucleic acid (RNA) virus contagious in humans and responsible for the ongoing coronavirus disease 2019 (COVID-19) [...].