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Men that carrierBRCA2germline mutations are at risk of developing prostate cancer. Here, the authors analyse the genomes of prostate cancer from these individuals and demonstrate increased genomic instability in comparison to sporadic prostate cancer.

The prognosis of castration-resistant prostate cancers remains dismal, but accurate preclinical models can lead to effective therapies. Here the Melbourne Urological Research Alliance establish prostate cancer patient-derived xenografts, use the tumors for organoids and single-cell RNA-seq, and show the efficacy of PARP inhibitor combination treatments.

Robust preclinical models of prostate cancer are required as clinical management of men with this disease evolves, and increasing genomic understanding makes currently available cell lines less relevant. A novel orthotopic xenograft mouse model is state of the art for preclinical models of prostate cancer.

This Perspective covers existing patient-derived xenografts (PDXs) of prostate cancer, and their features and uses in basic and preclinical research. The authors also discuss the need for additional PDXs, and how collaboration in prostate cancer PDX research can be improved.

A role for oestrogen has been implicated in the development of prostate cancer, but this role is complex. Should selective oestrogen-receptor modulators in conjunction with contemporary androgen-ablation therapy be used to treat this disease?

This Opinion article discusses some key similarities between breast and prostate cancer, with a focus on hormone and hormone receptor involvement. Understanding the commonalities between these cancers will hopefully provide unique opportunities for therapy.

Although CAR T therapy has greatly improved the therapeutic prospects for haematological malignancies, it is not yet widely used for solid tumors, such as prostate cancer. Here, using prostate cancer patient-derived xenografts, the authors demonstrate the efficacy of CAR T cells specific for Lewis Y antigen when combined with low-dose carboplatin.

The role of the FOXA1 to FOXA2 switch in the regulation of the response to androgen receptor signalling inhibition and lineage plasticity in prostate cancer remains unclear. Here, the authors highlight the function of FOXA2 in rewiring AP-1 to induce differential transcriptional reprogramming and lineage plasticity.

A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.

Hypospadias is the second most common developmental abnormality in boys. Although prenatal exposure to endocrine disruptors and genetic susceptiblity are established causes of this abnormality, the aetiology remains unknown in most cases. Here Cunha et al. describe current animal models of hypospadias, highlighting the differences between mouse, rat and human penile development and hypospadias, and the need for reliable, accurate and appropriate animal models.

Prostate cancer (PrCa) involves a large heritable genetic component. Here, the authors perform multivariate fine-mapping of known PrCa GWAS loci, identifying variants enriched for biological function, explaining more familial relative risk, and with potential application in clinical risk profiling.

The PSA (KLK3) genetic variant rs17632542 is associated with reduced prostate cancer risk and lower serum PSA levels, although the underlying reasons are unclear. Here, the authors show that this PSA variant reduced proteolytic activity and leads to smaller tumours, but also increases invasion and bone metastasis, indicating its dual risk association depending on tumour context; the variant is associated with both lower risk and poor clinical outcomes.

A multi-ancestry genome-wide association study of prostate cancer performed in 156,319 cases and 788,443 controls identifies 187 novel risk variants associated with the disease. Genetic risk scores associated with overall risk, and risk of aggressive disease in men of African ancestry.

In the localized prostate cancer setting, germline BRCA2 mutations confer aggressive clinicopathological features and poor outcomes. This Review discusses the clinical influence of BRCA2 mutations in localized disease, highlighting biological insights into disease aggressiveness from genomic studies and preclinical models.

An increasing number of men with low-risk prostate cancer are being managed using active surveillance, often resulting in improved quality of life compared with men who receive treatment for low-risk disease. However, strategies that might delay disease progression and the need for treatment are currently lacking. In this Review, the authors describe the potential of exercise-based interventions to delay the progression of low-risk prostate cancer.

A large meta-analysis combining genome-wide and custom high-density genotyping array data identifies 63 new susceptibility loci for prostate cancer, enhancing fine-mapping efforts and providing insights into the underlying biology.

Chromosome 8q24 is known to be a major susceptibility region for prostate cancer risk. Here the authors analyze genetic data across the 8q24 region from 71,535 prostate cancer patients identifying 12 risk loci, three previously unreported, highlighting the contribution of germline variation at this locus.

Age at voice-breaking is used to determine puberty timing in men, recall of which is considered less accurate than age at first menarche in women. Here, the authors perform multi-trait GWAS for male puberty timing by including both age at voice breaking and age of first facial hair for improved phenotype definition and power.

McGovern et al. establish an orthotopic, humanized prostate cancer model to study bone metastasis. The authors demonstrate that a humanized tumor microenvironment (TME) influences the metastatic spread of cancer cells to tissue-engineered bone, highlighting the importance of the TME in prostate cancer metastasis to bone.