Clinical Features and Therapeutic Outcomes in Men with Advanced Prostate Cancer and DNA Mismatch Repair Gene Mutations

Emmanuel S. Antonarakis; Farah Shaukat; Pedro Isaacsson Velho; Harsimar Kaur; Eugene Shenderov; Drew M. Pardoll; Tamara L. Lotan

doi:10.1016/j.eururo.2018.10.009

Clinical Features and Therapeutic Outcomes in Men with Advanced Prostate Cancer and DNA Mismatch Repair Gene Mutations

Emmanuel S. Antonarakis, Farah Shaukat, Pedro Isaacsson Velho, Harsimar Kaur, Eugene Shenderov, Drew M. Pardoll, Tamara L. Lotan

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

91 Scopus citations

Abstract

Despite aggressive clinicopathological features, mismatch repair (MMR)-mutated advanced prostate cancers are exquisitely responsive to standard and next-generation hormonal therapies, and also demonstrate anecdotal sensitivity to PD-1 inhibitors. Moreover, the presence of certain histological features (Gleason sum 9 or 10, and intraductal carcinoma) should prompt genomic evaluation of MMR deficiency, which is an actionable finding given the Food and Drug Administration's approval of pembrolizumab in this context.

Original language	English (US)
Pages (from-to)	378-382
Number of pages	5
Journal	European Urology
Volume	75
Issue number	3
DOIs	https://doi.org/10.1016/j.eururo.2018.10.009
State	Published - Mar 2019
Externally published	Yes

Bibliographical note

Funding Information:
Funding/Support and role of the sponsor : This work was partially supported by National Institutes of Health Cancer Center Support Grant P30 CA006973 (E.S.A. and T.L.L.), Department of Defense grant W81XWH-16-PCRP-CCRSA (E.S.A.), and the Bloomberg-Kimmel Institute for Cancer Immunotherapy (E.S.A., E.S., and D.M.P.).

Funding Information:
Financial disclosures: Emmanuel S. Antonarakis certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Emmanuel S. Antonarakis is a paid consultant/advisor to Janssen, Astellas, Sanofi, Dendreon, Medivation, ESSA, AstraZeneca, Clovis, and Merck; he has received research funding to his institution from Janssen, Johnson & Johnson, Sanofi, Dendreon, Genentech, Novartis, Tokai, Bristol Myers-Squibb, AstraZeneca, Clovis, and Merck; and he is the co-inventor of a biomarker technology that has been licensed to Qiagen. Tamara L. Lotan is a paid consultant/advisor to Janssen and has received research funding from Ventana/Roche.

Publisher Copyright:
© 2018 European Association of Urology

Keywords

MSH2
MSH6
Microsatellite instability
Mismatch repair
Prostate cancer

UN SDGs

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

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10.1016/j.eururo.2018.10.009

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title = "Clinical Features and Therapeutic Outcomes in Men with Advanced Prostate Cancer and DNA Mismatch Repair Gene Mutations",

abstract = "Despite aggressive clinicopathological features, mismatch repair (MMR)-mutated advanced prostate cancers are exquisitely responsive to standard and next-generation hormonal therapies, and also demonstrate anecdotal sensitivity to PD-1 inhibitors. Moreover, the presence of certain histological features (Gleason sum 9 or 10, and intraductal carcinoma) should prompt genomic evaluation of MMR deficiency, which is an actionable finding given the Food and Drug Administration's approval of pembrolizumab in this context.",

keywords = "MSH2, MSH6, Microsatellite instability, Mismatch repair, Prostate cancer",

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note = "Funding Information: Funding/Support and role of the sponsor : This work was partially supported by National Institutes of Health Cancer Center Support Grant P30 CA006973 (E.S.A. and T.L.L.), Department of Defense grant W81XWH-16-PCRP-CCRSA (E.S.A.), and the Bloomberg-Kimmel Institute for Cancer Immunotherapy (E.S.A., E.S., and D.M.P.). Funding Information: Financial disclosures: Emmanuel S. Antonarakis certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Emmanuel S. Antonarakis is a paid consultant/advisor to Janssen, Astellas, Sanofi, Dendreon, Medivation, ESSA, AstraZeneca, Clovis, and Merck; he has received research funding to his institution from Janssen, Johnson & Johnson, Sanofi, Dendreon, Genentech, Novartis, Tokai, Bristol Myers-Squibb, AstraZeneca, Clovis, and Merck; and he is the co-inventor of a biomarker technology that has been licensed to Qiagen. Tamara L. Lotan is a paid consultant/advisor to Janssen and has received research funding from Ventana/Roche. Publisher Copyright: {\textcopyright} 2018 European Association of Urology",

year = "2019",

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doi = "10.1016/j.eururo.2018.10.009",

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volume = "75",

pages = "378--382",

journal = "European Urology",

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AU - Isaacsson Velho, Pedro

AU - Kaur, Harsimar

AU - Shenderov, Eugene

AU - Pardoll, Drew M.

AU - Lotan, Tamara L.

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AB - Despite aggressive clinicopathological features, mismatch repair (MMR)-mutated advanced prostate cancers are exquisitely responsive to standard and next-generation hormonal therapies, and also demonstrate anecdotal sensitivity to PD-1 inhibitors. Moreover, the presence of certain histological features (Gleason sum 9 or 10, and intraductal carcinoma) should prompt genomic evaluation of MMR deficiency, which is an actionable finding given the Food and Drug Administration's approval of pembrolizumab in this context.

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KW - Prostate cancer

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Clinical Features and Therapeutic Outcomes in Men with Advanced Prostate Cancer and DNA Mismatch Repair Gene Mutations

Abstract

Bibliographical note

Keywords

UN SDGs

Publisher link

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