Abstract
Molecular-targeted therapies and treatment stratification based on molecular biomarkers have rapidly gained momentum in the therapeutic spectrum for patients with prostate cancer, particularly those with aggressive disease. DNA damage repair (DDR) pathways are commonly impaired in prostate cancer. Recent studies have detailed mechanisms interconnecting the DDR with the androgen receptor (AR) signaling pathway as well as its interplay with the immune response. The prominent role of DDR deficiency in prostate cancer development and treatment response encourages innovative strategies for the detection of DDR deficiency in individual tumors. In this review, we describe recent preclinical and early clinical data on the exploitation of DDR defects as predictive biomarkers and also as molecular therapeutic targets.
Keywords:
DNA damage response; molecular biomarker; prostate cancer; targeted therapy.
Copyright © 2020 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Androgen Antagonists / pharmacology
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Androgen Antagonists / therapeutic use
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Antineoplastic Combined Chemotherapy Protocols / pharmacology*
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Biomarkers, Tumor / antagonists & inhibitors
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Biomarkers, Tumor / genetics*
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Chemoradiotherapy / methods*
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DNA Repair / drug effects*
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DNA Repair / radiation effects
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Drug Resistance, Neoplasm / drug effects
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Drug Resistance, Neoplasm / genetics
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Humans
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Immune Checkpoint Inhibitors / pharmacology
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Immune Checkpoint Inhibitors / therapeutic use
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Male
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Molecular Targeted Therapy / methods
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Mutation
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Prognosis
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Prostatic Neoplasms / genetics*
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Prostatic Neoplasms / immunology
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Prostatic Neoplasms / pathology
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Prostatic Neoplasms / therapy
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Radiation Tolerance / drug effects
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Radiation Tolerance / genetics
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Receptors, Androgen / metabolism
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Signal Transduction / drug effects
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Signal Transduction / genetics
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Signal Transduction / immunology
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Signal Transduction / radiation effects
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Treatment Outcome
Substances
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AR protein, human
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Androgen Antagonists
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Biomarkers, Tumor
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Immune Checkpoint Inhibitors
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Receptors, Androgen