Cargando…
Treatment-emergent neuroendocrine prostate cancer with a germline BRCA2 mutation: identification of a candidate reversion mutation associated with platinum/PARP-inhibitor resistance
Neuroendocrine prostate cancer (NEPC) is a highly aggressive histologic subtype of prostate cancer associated with a poor prognosis. Its incidence is expected to increase as castration-resistant disease emerges from the widespread use of potent androgen receptor-targeting therapies, such as abirater...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903888/ https://www.ncbi.nlm.nih.gov/pubmed/33608381 http://dx.doi.org/10.1101/mcs.a005801 |
Sumario: | Neuroendocrine prostate cancer (NEPC) is a highly aggressive histologic subtype of prostate cancer associated with a poor prognosis. Its incidence is expected to increase as castration-resistant disease emerges from the widespread use of potent androgen receptor-targeting therapies, such as abiraterone and enzalutamide. Defects in homologous recombination repair genes, such as BRCA1/2, are also being increasingly detected in individuals with advanced prostate cancer. We present the case of a 65-yr-old man with a germline BRCA2 mutation who developed explosive treatment-emergent, small-cell neuroendocrine prostate cancer. He achieved a complete response to platinum-containing chemotherapy, but a limited remission duration with the use of olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, as maintenance therapy. Upon relapse, tumor genomic profiling revealed a novel 228-bp deletion in exon 11 of the BRCA2 gene. The addition of the anti-PD1 drug pembrolizumab to olaparib was ineffective. This case highlights the ongoing challenges in treating neuroendocrine prostate cancer, even in the setting of homologous recombination repair deficiency. |
---|