Germline DNA-repair Gene Mutations and Outcomes in Men with Metastatic Castration-resistant Prostate Cancer Receiving First-line Abiraterone and Enzalutamide

Emmanuel S. Antonarakis; Changxue Lu; Brandon Luber; Chao Liang; Hao Wang; Yan Chen; John L. Silberstein; Danilo Piana; Zhao Lai; Yidong Chen; William B. Isaacs; Jun Luo

doi:10.1016/j.eururo.2018.01.035

Germline DNA-repair Gene Mutations and Outcomes in Men with Metastatic Castration-resistant Prostate Cancer Receiving First-line Abiraterone and Enzalutamide

Emmanuel S. Antonarakis, Changxue Lu, Brandon Luber, Chao Liang, Hao Wang, Yan Chen, John L. Silberstein, Danilo Piana, Zhao Lai, Yidong Chen, William B. Isaacs, Jun Luo

Research output: Contribution to journal › Article › peer-review

130 Scopus citations

Abstract

To determine whether and how germline DNA-repair gene mutations influence clinical outcomes to abiraterone or enzalutamide in patients with castration-resistant prostate cancer (CRPC), we performed germline genotyping for 50 DNA-repair genes using blood samples from 172 patients with CRPC beginning first-line systemic therapy with abiraterone or enzalutamide. We discovered that the presence of germline DNA-repair gene defects (particularly mutations in the BRCA1/2 and ATM genes) were associated with better outcomes to abiraterone and enzalutamide.

Original language	English (US)
Pages (from-to)	218-225
Number of pages	8
Journal	European Urology
Volume	74
Issue number	2
DOIs	https://doi.org/10.1016/j.eururo.2018.01.035
State	Published - Aug 2018
Externally published	Yes

Bibliographical note

Funding Information:
Funding/Support and role of the sponsor: This work is supported by National Institutes of Health Grants R01 CA185297 and P30 CA006973, Department of Defense Prostate Cancer Research Program Grants W81XWH-15-2-0050 and W81XWH-12-1-0605, the Commonwealth Fund, and Johns Hopkins Prostate SPORE Grant P50 CA058236, and by the Patrick C. Walsh Fund and the Prostate Cancer Foundation. The sponsors played no direct role in the study.

Keywords

Abiraterone
DNA repair
Enzalutamide
Germline
Mutation

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.eururo.2018.01.035

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Antonarakis, E. S., Lu, C., Luber, B., Liang, C., Wang, H., Chen, Y., Silberstein, J. L., Piana, D., Lai, Z., Chen, Y., Isaacs, W. B., & Luo, J. (2018). Germline DNA-repair Gene Mutations and Outcomes in Men with Metastatic Castration-resistant Prostate Cancer Receiving First-line Abiraterone and Enzalutamide. European Urology, 74(2), 218-225. https://doi.org/10.1016/j.eururo.2018.01.035

Antonarakis, ES, Lu, C, Luber, B, Liang, C, Wang, H, Chen, Y, Silberstein, JL, Piana, D, Lai, Z, Chen, Y, Isaacs, WB & Luo, J 2018, 'Germline DNA-repair Gene Mutations and Outcomes in Men with Metastatic Castration-resistant Prostate Cancer Receiving First-line Abiraterone and Enzalutamide', European Urology, vol. 74, no. 2, pp. 218-225. https://doi.org/10.1016/j.eururo.2018.01.035

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abstract = "To determine whether and how germline DNA-repair gene mutations influence clinical outcomes to abiraterone or enzalutamide in patients with castration-resistant prostate cancer (CRPC), we performed germline genotyping for 50 DNA-repair genes using blood samples from 172 patients with CRPC beginning first-line systemic therapy with abiraterone or enzalutamide. We discovered that the presence of germline DNA-repair gene defects (particularly mutations in the BRCA1/2 and ATM genes) were associated with better outcomes to abiraterone and enzalutamide.",

keywords = "Abiraterone, DNA repair, Enzalutamide, Germline, Mutation",

author = "Antonarakis, {Emmanuel S.} and Changxue Lu and Brandon Luber and Chao Liang and Hao Wang and Yan Chen and Silberstein, {John L.} and Danilo Piana and Zhao Lai and Yidong Chen and Isaacs, {William B.} and Jun Luo",

note = "Funding Information: Funding/Support and role of the sponsor: This work is supported by National Institutes of Health Grants R01 CA185297 and P30 CA006973, Department of Defense Prostate Cancer Research Program Grants W81XWH-15-2-0050 and W81XWH-12-1-0605, the Commonwealth Fund, and Johns Hopkins Prostate SPORE Grant P50 CA058236, and by the Patrick C. Walsh Fund and the Prostate Cancer Foundation. The sponsors played no direct role in the study. ",

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doi = "10.1016/j.eururo.2018.01.035",

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AU - Lu, Changxue

AU - Luber, Brandon

AU - Liang, Chao

AU - Wang, Hao

AU - Chen, Yan

AU - Silberstein, John L.

AU - Piana, Danilo

AU - Lai, Zhao

AU - Chen, Yidong

AU - Isaacs, William B.

AU - Luo, Jun

N1 - Funding Information: Funding/Support and role of the sponsor: This work is supported by National Institutes of Health Grants R01 CA185297 and P30 CA006973, Department of Defense Prostate Cancer Research Program Grants W81XWH-15-2-0050 and W81XWH-12-1-0605, the Commonwealth Fund, and Johns Hopkins Prostate SPORE Grant P50 CA058236, and by the Patrick C. Walsh Fund and the Prostate Cancer Foundation. The sponsors played no direct role in the study.

PY - 2018/8

Y1 - 2018/8

N2 - To determine whether and how germline DNA-repair gene mutations influence clinical outcomes to abiraterone or enzalutamide in patients with castration-resistant prostate cancer (CRPC), we performed germline genotyping for 50 DNA-repair genes using blood samples from 172 patients with CRPC beginning first-line systemic therapy with abiraterone or enzalutamide. We discovered that the presence of germline DNA-repair gene defects (particularly mutations in the BRCA1/2 and ATM genes) were associated with better outcomes to abiraterone and enzalutamide.

AB - To determine whether and how germline DNA-repair gene mutations influence clinical outcomes to abiraterone or enzalutamide in patients with castration-resistant prostate cancer (CRPC), we performed germline genotyping for 50 DNA-repair genes using blood samples from 172 patients with CRPC beginning first-line systemic therapy with abiraterone or enzalutamide. We discovered that the presence of germline DNA-repair gene defects (particularly mutations in the BRCA1/2 and ATM genes) were associated with better outcomes to abiraterone and enzalutamide.

KW - Abiraterone

KW - DNA repair

KW - Enzalutamide

KW - Germline

KW - Mutation

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Germline DNA-repair Gene Mutations and Outcomes in Men with Metastatic Castration-resistant Prostate Cancer Receiving First-line Abiraterone and Enzalutamide

Abstract

Bibliographical note

Keywords

UN SDGs

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