Dear Colleagues,

Prostate cancer is the second most common neoplasm in men worldwide and the second leading cause of cancer deaths in Western countries. Due to the large-scale sequencing efforts, there is a better understanding of the genomic landscape of prostate cancer. Within this context, recurrent somatic mutations, copy number alterations, and oncogenic structural DNA rearrangements have been identified. These include point mutations in SPOP, FOXA1, and TP53; copy number alterations involving MYC, RB1, PTEN, and CHD1; and E26 transformation-specific (ETS) fusions. Data on mechanisms of DNA repair and experimental evidence still represent an urgent need. The identification of genomic defects in DNA repair has already led to clinical studies that provide a strong rationale for developing poly (ADP-ribose) polymerase (PARP) inhibitors and DNA-damaging agents in this molecularly defined subset of patients.

Carriers of BRCA2 pathogenic sequence variants (PSVs) have increased levels of serum prostate specific antigen (PSA) at diagnosis, increased proportion of high Gleason tumors, elevated rates of nodal and distant metastases, and a high recurrence rate. BRCA2 PSVs confer lower overall survival. The association of BRCA1 and prostate cancer has not been replicated in all studies. The National Comprehensive Cancer Network guidelines recommend that BRCA2 carriers should begin PSA screening at 45 years of age, while BRCA1 carriers should be advised to consider it. The IMPACT study evaluated a tailored prostate cancer screening in men with BRCA1/2 germline mutation and proposed annual PSA tests and a prostate biopsy if PSA >3 ng/mL.

In this editorial, we highlight the biology of deleterious inherited or acquired DNA repair pathway aberrations in prostate cancer. The manuscripts should be focused on but are not only limited to:

• Prostate risk assessment in the era of next-generation sequencing;
• Prognostic biomarkers in metastatic castration-resistant prostate cancer;
• Molecular signatures in prostate cancer;
• Aberrations of DNA repair pathways in prostate cancer;
• Germline genetic variants in prostate cancer;
• PARP inhibitors in prostate cancer;
• Targeting androgen receptor activity in prostate cancer;
• Resistance to androgen receptor targeting therapies in prostate cancer;
• Anti-angiogenesis in prostate cancer.

Dr. Stergios Boussios
Guest Editor

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• prostate cancer
• cancer screening
• tumor microenvironment
• molecular pathogenesis
• biomarkers
• liquid biopsies
• PSA
• androgens
• androgen receptor
• castration resistance
• precision medicine