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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...

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Autores principales: Pandya, Deep, Shah, Myra, Kaplan, Fuat, Martino, Candice, Levy, Gillian, Kazanjian, Mia, Batter, Stephen, Martignetti, John, Frank, Richard C.
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
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author Pandya, Deep
Shah, Myra
Kaplan, Fuat
Martino, Candice
Levy, Gillian
Kazanjian, Mia
Batter, Stephen
Martignetti, John
Frank, Richard C.
author_facet Pandya, Deep
Shah, Myra
Kaplan, Fuat
Martino, Candice
Levy, Gillian
Kazanjian, Mia
Batter, Stephen
Martignetti, John
Frank, Richard C.
author_sort Pandya, Deep
collection PubMed
description 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.
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spelling pubmed-79038882021-03-09 Treatment-emergent neuroendocrine prostate cancer with a germline BRCA2 mutation: identification of a candidate reversion mutation associated with platinum/PARP-inhibitor resistance Pandya, Deep Shah, Myra Kaplan, Fuat Martino, Candice Levy, Gillian Kazanjian, Mia Batter, Stephen Martignetti, John Frank, Richard C. Cold Spring Harb Mol Case Stud Research Report 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. Cold Spring Harbor Laboratory Press 2021-02 /pmc/articles/PMC7903888/ /pubmed/33608381 http://dx.doi.org/10.1101/mcs.a005801 Text en © 2021 Pandya et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/) , which permits reuse and redistribution, except for commercial purposes, provided that the original author and source are credited.
spellingShingle Research Report
Pandya, Deep
Shah, Myra
Kaplan, Fuat
Martino, Candice
Levy, Gillian
Kazanjian, Mia
Batter, Stephen
Martignetti, John
Frank, Richard C.
Treatment-emergent neuroendocrine prostate cancer with a germline BRCA2 mutation: identification of a candidate reversion mutation associated with platinum/PARP-inhibitor resistance
title Treatment-emergent neuroendocrine prostate cancer with a germline BRCA2 mutation: identification of a candidate reversion mutation associated with platinum/PARP-inhibitor resistance
title_full Treatment-emergent neuroendocrine prostate cancer with a germline BRCA2 mutation: identification of a candidate reversion mutation associated with platinum/PARP-inhibitor resistance
title_fullStr Treatment-emergent neuroendocrine prostate cancer with a germline BRCA2 mutation: identification of a candidate reversion mutation associated with platinum/PARP-inhibitor resistance
title_full_unstemmed Treatment-emergent neuroendocrine prostate cancer with a germline BRCA2 mutation: identification of a candidate reversion mutation associated with platinum/PARP-inhibitor resistance
title_short Treatment-emergent neuroendocrine prostate cancer with a germline BRCA2 mutation: identification of a candidate reversion mutation associated with platinum/PARP-inhibitor resistance
title_sort treatment-emergent neuroendocrine prostate cancer with a germline brca2 mutation: identification of a candidate reversion mutation associated with platinum/parp-inhibitor resistance
topic Research Report
url 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
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