Research round up from the clinic - top four articles from July 2015:
1. Could targeting the protein DNA-PKcs prevent the spread of prostate cancer?
In this study, Goodwin et al. aimed to determine the molecular basis of DNA-PKcs function and the contribution of DNA-PKcs-mediated transcriptional regulation on tumour phenotypes. The DNA-dependent protein kinase (DNA-PK) is composed of two units, including a catalytic subunit (DNA-PKcs) that plays an important role in the DNA damage response and maintenance of genomic stability. This research, which was carried out in the United States, involved mouse models and clinical analysis of tumour samples from 232 patients. Samples were obtained using a case-cohort study design to randomly sample 20% of patients for analysis, in addition to all in whom metastases developed, from a cohort of 1,010 high-risk men who underwent radical prostatectomy between 2000 and 2006.
The authors identified DNA-PKcs as a key contributor to metastatic progression, and the findings support a model wherein the transcriptional regulatory functions of DNA-PKcs induce a signalling program that drives tumour metastases and lethal disease. Dr Iain Frame, director of research at Prostate Cancer UK said “Getting to grips with how and why cancer cells spread around the body is one of the biggest challenges we face today. The answer to this question will allow us to not only predict which early stage prostate cancers may go on to spread and become dangerous, but also develop new treatments to stop the cells spreading in the first place. Although this research could provide us with some of the answers we desperately need, it's still early days. We look forward to further results of this trial and hope they lead to better ways to prevent and treat advanced prostate cancer.”
2. Are surveillance strategies effective for men with low-risk prostate cancer?
Many men diagnosed with localised, low-risk prostate cancer, which may not be lethal, undergo primary treatment with surgery or radiation. These treatments can affect health-related quality of life (HRQOL), including longstanding side effects such as erectile dysfunction and impaired urinary function. This review, by Filson and colleagues from UCLA in the United States, describes the current surveillance protocols (e.g. active surveillance and watchful waiting), and reviews the outcomes for each of these strategies in terms of cancer survival and quality of life. Additionally the review addresses the novel technologies such as prostate MRI and fusion biopsies that may prove beneficial for surveillance patients.
The authors concluded active surveillance and expectant management strategies can produce excellent long-term disease-specific survival and minimal morbidity for men with prostate cancer. Questions remain regarding both the identification of optimal candidates for surveillance, as well as understanding the ideal monitoring strategy. Despite increased adoption of expectant management, active surveillance still remains broadly underused and more data will be needed to clarify the factors contributing to the findings of the review at a population level.
3. Novel Biomarker Signature may predict aggressive prostate cancer in African-Americans
Researchers from the United States and Canada evaluated whether genetic factors could affect ethnic disparities in prostate cancer development and disease progression. The study looked at the ethnicity-specific expression of 20 prostate cancer-associated biomarkers in 154 African Americans and 243 European American patients. The researchers analysed these samples to find out which of the 20 validated genes—some of which initiate and some which drive cancer - were expressed in high or low quantities in the two populations of men. The authors identified a subtype which they called "triple negative prostate cancer," and defined as the absence or low levels of three genes called ERG, ETS, and SPINK1.
They reported African American men with high disease severity and risk of recurrence (this was calculated using a validated scoring system known as CAPRA-S) and more advanced Gleason grade disease at diagnosis were more likely to be triple negative when compared to European American men with a similar disease scores at diagnosis. In addition, the researchers also found other genes that were expressed at different levels in African American versus European American men. Further studies are already underway to validate the significance of this trend. The authors concluded that the subset of prostate cancer biomarkers they identified may explain in part the biologic contribution to ethnic disparity in prostate cancer outcomes between African American and European American men. In a clinical setting, it may suggest that some African American men with prostate cancer might have a better shot at survival if they are treated with a different approach than standard of care, however more research and investigation is required to refine the biomarkers that will capture these differences and develop approaches that help reduce the disparities in outcomes.
4. Black men are twice as likely to die from prostate cancer as white men
A study recently published in BMC Medicine, by researchers at Prostate Cancer UK and Public Health England, looked at the absolute risk figures to help men of different ethnicities better understand their risk of being diagnosed with, and dying from, prostate cancer. Previous research has estimated that a UK man’s lifetime risk of being diagnosed with prostate cancer is 1 in 8, and prostate cancer incidence rate data in England shows that Black men are significantly more likely, and Asian men significantly less likely, to be diagnosed with the disease compared to White men. The authors of this current study analysed prostate cancer incidence and mortality data of over 100,000 men, along with population and ethnicity figures from a combination of sources, to calculate the lifetime risk of being diagnosed with, and dying from, prostate cancer by ethnic group.
The study reported the lifetime risk of being diagnosed with prostate cancer is approximately 1 in 4 for Black men, 1 in 8 for white men and 1 in 13 for Asian men. In addition, the article reports the lifetime risk of dying from prostate cancer – approximately 1 in 12 for Black men, 1 in 24 for White men and 1 in 44 for Asian men. The authors conclude the findings should be used for targeted awareness-raising, but raise the fact that other risk factors can also affect an individual man’s risk of prostate cancer (including family history, weight and age). In addition, they recommend that further work is needed to understand the mechanisms behind the higher than average risk in Black men.