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Prostate Cancer pp 279–300Cite as

Germline and Somatic Defects in DNA Repair Pathways in Prostate Cancer

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1210))

Abstract

Recent studies have provided a better understanding of the molecular underpinnings of prostate cancer. Alterations in genes encoding for proteins involved in the different pathways in charge of preserving genomic integrity and repairing DNA damage are common in prostate cancer, particularly in late-stage disease. Generally, these alterations would confer a survival advantage for tumors, resulting in a more aggressive phenotype. However, DNA repair defects can also represent a vulnerability for tumors that can be exploited therapeutically, offering the possibility of precision medicine strategies. Moreover, many of these mutations are linked to hereditary risk for cancers; hence, identification of DNA repair mutations could also be relevant for cancer prevention and screening in healthy individuals, including relatives of prostate cancer patients. In this chapter, we summarize current knowledge about the prevalence of different DNA repair gene alterations across different stages of prostate cancer and review the clinical relevance of such events in terms of prognosis and treatment stratification.

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Abbreviations

ADT:

Androgen deprivation therapy

alt-NHEJ:

Alternative non-homologous end joining pathway

AP:

Apurinic-apyrimidinic sites

AR:

Androgen receptor

BER:

Base Excision Repair

CRPC:

Castration-resistant prostate cancer

DDR:

DNA damage repair

DSB:

Double strand break

ETS:

E26 transformation-specific

GG-NER:

Global genome NER pathways

HR:

Homologous recombination, or Hazard Ratio

ICI:

Immune checkpoint inhibitors

IR:

Ionizing radiation

mCRPC:

Metastatic castration resistant prostate cancer

MMR:

Mismatch DNA Repair

NEPC:

Neuroendocrine prostate cancer

NER:

Nucleotide Excision Repair

NGS:

Next-generation sequencing

NHEJ:

Non-homologous end joining

PARP:

Poly(ADP) ribose polymerase

PCF:

Prostate Cancer Foundation

PFS:

Progression-free survival

ROS:

Reactive oxygen species

SNP:

Single nucleotide polymorphism

SSB:

Single strand break

SU2C:

Stand-up-to-Cancer

TC-NER:

Transcription-coupled NER

UV:

Ultraviolet

UV-DDB:

Ultraviolet damaged DNA-binding protein

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Authors and Affiliations

  1. Vall d’Hebron Institute of Oncology, Barcelona, Spain

    Sara Arce, Alejandro Athie & Joaquin Mateo

  2. University of Washington, Seattle, WA, USA

    Colin C. Pritchard

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  1. Sara Arce
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  2. Alejandro Athie
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  3. Colin C. Pritchard
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  4. Joaquin Mateo
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Correspondence to Joaquin Mateo .

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Editors and Affiliations

  1. Department of Laboratory Medicine and Pathology, Department of Urology, Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA

    Scott M. Dehm

  2. Departments of Urology, and Biochemistry & Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN, USA

    Donald J. Tindall

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Arce, S., Athie, A., Pritchard, C.C., Mateo, J. (2019). Germline and Somatic Defects in DNA Repair Pathways in Prostate Cancer. In: Dehm, S., Tindall, D. (eds) Prostate Cancer. Advances in Experimental Medicine and Biology, vol 1210. Springer, Cham. https://doi.org/10.1007/978-3-030-32656-2_12

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