What's new?

The androgen receptor (AR) is a key factor in prostate cancer (PCa) progression and metastasis. Given that matrix metalloproteinase 9 (MMP9) and the vascular endothelial growth factor (VEGF) pathway are critical for tumor vascularization and invasion under castration-resistant condition, it may be of importance to define the functional interplay between AR and MMP9 and their associated key survival and invasion pathways in PCa cells. This study identifies novel cooperative mechanisms involving AR, the MMP9/ VEGF signaling axis and PIP5K1α/AKT pathways driving tumor invasion. The findings provide new information to guide the development of targeted therapy for invasive castration-resistant prostate cancer.

What's new?

Long-term survival to 15 years among germ cell testicular cancer survivors treated in the cisplatin era, marked by the introduction of cisplatin in the late 1970s, generally has been excellent. Beyond 20 years, however, survival rates decline. In this analysis of data on Norwegian men diagnosed with testicular cancer between 1980 and 2009, an increased overall risk for nongerm cell second cancer was detected among survivors, despite treatment. Risk was elevated in particular beyond 10 years of follow-up after cisplatin-based chemotherapy or radiotherapy. Despite reduced treatment intensity, two or more cycles of cisplatin-based chemotherapy was associated with continuing increased second cancer risk.

What's new?

Family history is among the strongest known risk factors for prostate cancer (PCa). Despite progress in defining molecular subtypes of PCa, little is known about their heritability. Here, the authors examine associations between family history and incidence of PCa defined by fusions of androgen-regulated promoters with ERG and, separately, PTEN loss in 44,126 men from the prospective Health Professionals Follow-up Study. The results indicate that family history may be positively associated with PCa in all ERG and PTEN subtypes, suggesting a role for genetic susceptibility in their development. Furthermore, ERG-negative disease could potentially be especially associated with positive family history.

What's new?

There is strong evidence for a genetic predisposition to prostate cancer (PrCa). Most of this information has come from European ancestry populations, with Latinos representing less than 1% of samples in cancer genome-wide association studies (GWAS). In this study, the majority of established PrCa risk variants (83.3%) were consistently associated with PrCa risk in Latinos. A polygenic risk score comprised of GWAS-identified risk variants could identify 10% of Latino men with a ~three-fold increase in PrCa risk. These findings suggest that common germline variants for PrCa can stratify risk in Latino men, which has implications for targeted screening and prevention.

What's new?

Metastasis-directed therapy (MDT), involving surgery or stereotactic ablative radiotherapy, is a promising alternative treatment strategy for prostate cancer patients with metastatic disease. It remains unclear, however, which subsets of patients most benefit from MDT. Here, interim analysis of a large prospective trial involving fractionated stereotactic body radiotherapy (SBRT) for prostate cancer patients with up to five synchronous oligometastases shows that 2 years following SBRT, about half of patients did not require treatment escalation. In addition, nearly one-quarter of patients had prostate-specific antigen levels below baseline. The findings highlight the promise of SBRT for long-term suppression of oligometastatic prostate cancer.

What's new?

Although localized prostate cancer (PC) can be cured by radical prostatectomy (RP), both over- and under-treatment remain a major clinical problem as currently available routine prognostic tools cannot accurately distinguish aggressive from non-aggressive PCs at time of diagnosis. Here, the authors report a novel combined miRNA/methylation marker panel (miMe) for PC prognosis that was a significant independent predictor of post-operative PC outcome in three large RP cohorts. The results suggest that miMe may help guide personalized treatment decisions in the future, e.g. by identifying high-risk PC patients who might be candidates for intensified therapy.