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Urinary PGE-M is a stable metabolite of prostaglandin E2 (PGE2). PGE2 is a product of the inflammatory COX signaling pathway and has been associated with cancer incidence and metastasis. Its synthesis can be inhibited by aspirin. We investigated the association of PGE-M with lethal prostate cancer in a case–control study of African American (AA) and European American men. We measured urinary PGE-M using mass-spectrometry. Samples were obtained from 977 cases and 1022 controls at the time of recruitment. We applied multivariable logistic and Cox regression modeling to examine associations of PGE-M with prostate cancer and participant survival. Median survival follow-up was 8.4 years, with 246 deaths among cases. Self-reported aspirin use over the past 5 years was assessed with a questionnaire. Race/ethnicity was self-reported. Urinary PGE-M levels did not differ between men with prostate cancer and population-based controls. We observed no association between PGE-M and aggressive disease nor prostate-cancer-specific survival. However, we observed a statistically significant association between higher (&gt, median) PGE-M and all-cause mortality in AA cases who did not regularly use aspirin (HR = 2.04, 95% CI 1.23–3.37). Among cases who reported using aspirin, there was no association. Our study does not support a meaningful association between urinary PGE-M and prostate cancer. Moreover, PGE-M levels were not associated with aggressive prostate cancer. However, the observed association between elevated PGE-M and all-cause mortality in AA non-aspirin users reinforces the potential benefit of aspirin to reduce mortality among AA men with prostate cancer.

Simple Summary Men of African descent are twice as likely to die of prostate cancer than other men. While equal access to care is the key target to improve cancer survival, it is now known that there are differences in disease biology and risk factor exposure across population groups. These differences could be causatively linked to the existing prostate cancer health disparities. In this review, we will discuss the candidate role of inflammation and the immune response as contributing factors to the excessive burden of lethal prostate cancer among men of African ancestry. Furthermore, we will introduce the concept that these immunogenic vulnerabilities could be exploited to address the adverse outcomes experienced by these men. Lastly, we will summarize how these immunogenic and inflammatory differences could be targeted using current treatments to improve survival for men of African descent. Abstract Despite substantial improvements in cancer survival, not all population groups have benefitted equally from this progress. For prostate cancer, men of African descent in the United States and England continue to have about double the rate of fatal disease compared to other men. Studies suggest that when there is equal access to care, survival disparities are greatly diminished. However, notable differences exist in prostate tumor biology across population groups. Ancestral factors and disparate exposures can lead to altered tumor biology, resulting in a distinct disease etiology by population group. While equal care remains the key target to improve survival, additional efforts should be made to gain comprehensive knowledge of the tumor biology in prostate cancer patients of African descent. Such an approach may identify novel intervention strategies in the era of precision medicine. A growing body of evidence shows that inflammation and the immune response may play a distinct role in prostate cancer disparities. Low-grade chronic inflammation and an inflammatory tumor microenvironment are more prevalent in African American patients and have been associated with adverse outcomes. Thus, differences in activation of immune–inflammatory pathways between African American and European American men with prostate cancer may exist. These differences may influence the response to immune therapy which is consistent with recent observations. This review will discuss mechanisms by which inflammation may contribute to the disparate outcomes experienced by African American men with prostate cancer and how these immunogenic and inflammatory vulnerabilities could be exploited to improve their survival.

Conventional therapies for cancer such as chemotherapy and radiotherapy remain a mainstay in treatment, but in many cases a targeted approach is lacking, and patients can be vulnerable to drug resistance. In recent years, novel concepts have been emerging to improve the traditional therapeutic options in cancers with poor survival outcomes. New therapeutic strategies involving areas like energy metabolism and extracellular vesicles along with advances in immunotherapy and nanotechnology are driving the next generation of cancer treatments. The development of fields such as theranostics in nanomedicine is also opening new doors for targeted drug delivery and nano-imaging. Here we discuss the use of innovative technologies presented at the Irish Association for Cancer Research (IACR) Annual Meeting, highlighting examples of where new approaches may lead to promising new treatment options for a range of cancer types.