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Targeting DNA Repair Defects for Precision Medicine in Prostate Cancer

  • Genitourinary Cancers (DP Petrylak and JW Kim, Section Editors)
  • Published:
Current Oncology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Genomic studies of localized and metastatic prostate cancer have identified a high prevalence of clinically actionable alterations including mutations in DNA repair genes. In this manuscript, we review the current knowledge on DNA repair defects in prostate cancer and provide an overview of how these alterations can be targeted towards a personalized prostate cancer management.

Recent Findings

Twenty to 25% of metastatic prostate cancers harbor defects in DNA repair genes, most commonly in the homologous recombination genes. These defects confer increased sensitivity to platinum chemotherapy or poly (ADP-ribose) polymerase (PARP) inhibitors. Recent trials also support a synergistic effect of combining these therapies with androgen receptor-targeting agents. Identification of mismatch-repair defects could result in defining a prostate cancer population who may benefit from immune checkpoint inhibitors. These data have implications for family testing and early diagnosis, as many of these mutations are linked to inherited risk of prostate cancer.

Summary

The DNA damage repair pathways are clinically relevant in prostate cancer, being a target for precision medicine; combination with standard-of-care androgen receptor (AR)-targeting agents may be synergistic.

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Funding

J. Mateo is supported by a Prostate Cancer Foundation and has received research funding from Fundació Obra Social La Caixa, Cellex Foundation, FERO, Sociedad Española de Oncología Médica (SEOM) and the US Department of Defense.

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Authors and Affiliations

  1. Prostate Cancer Translational Research Group, Vall d’Hebron Institute of Oncology (VHIO), Cellex Center, Natzaret 115-117, 08035, Barcelona, Spain

    Alejandro Athie, Sara Arce-Gallego, Macarena Gonzalez, Rafael Morales-Barrera, Cristina Suarez, Teresa Casals Galobart, Gonzalo Hernandez Viedma, Joan Carles & Joaquin Mateo

  2. Department of Medical Oncology, Vall d’Hebron University Hospital, Barcelona, Spain

    Macarena Gonzalez, Rafael Morales-Barrera, Cristina Suarez, Joan Carles & Joaquin Mateo

Authors
  1. Alejandro Athie
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  2. Sara Arce-Gallego
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  3. Macarena Gonzalez
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  4. Rafael Morales-Barrera
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  5. Cristina Suarez
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  6. Teresa Casals Galobart
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  7. Gonzalo Hernandez Viedma
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  8. Joan Carles
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  9. Joaquin Mateo
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Corresponding author

Correspondence to Joaquin Mateo.

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Conflict of Interest

Alejandro Athie declares that he has no conflict of interest.

Sara Arce-Gallego declares that she has no conflict of interest.

Macarena Gonzalez has received compensation from Roche for service as a consultant/advisor and has received reimbursement for travel/accommodation expenses from Astellas, Bayer, and Lilly.

Rafael Morales-Barrera has received compensation from Sanofi Aventis, Bayer, Janssen, AstraZeneca, Merck Sharp & Dohme, and Asofarma for service as a consultant/advisor and has received reimbursement for travel/accommodation expenses from Roche, Sanofi Aventis, Astellas, Janssen, Merck Sharp & Dohme, Bayer, Pharmacyclics, Clovis Oncology, and Lilly.

Cristina Suarez has received compensation from Roche for service as a consultant, compensation from Bristol-Myers Squibb, Pfizer, and Ipsen for service on advisory boards and on speaker’s bureaus, and has received reimbursement for travel/accommodation expenses from Bristol-Myers Squibb, Pfizer, and Roche.

Teresa Casals Galobart declares that she has no conflict of interest.

Gonzalo Hernandez Viedma declares that he has no conflict of interest.

Joan Carles has received compensation from Bayer, Johnson & Johnson, Bristol-Myers Squibb, Astellas, Pfizer, Sanofi, MSD Oncology, Roche, and AstraZeneca for service on advisory boards and has received compensation from Bayer, Johnson & Johnson, Asofarma, and Astellas for service on speaker’s bureaus.

Joaquin Mateo has received compensation from AstraZeneca, Roche, and Janssen for service on advisory boards, compensation from Sanofi and Astellas for service on speaker’s bureaus, and has received reimbursement for travel/accommodation expenses from AstraZeneca.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Genitourinary Cancers

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Athie, A., Arce-Gallego, S., Gonzalez, M. et al. Targeting DNA Repair Defects for Precision Medicine in Prostate Cancer. Curr Oncol Rep 21, 42 (2019). https://doi.org/10.1007/s11912-019-0790-6

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