Abstract

BackgroundAfrican Americans (AAs) in the United States are known to have a higher incidence and mortality for Prostate Cancer (PCa). The drivers of this epidemiological disparity are multifactorial, including socioeconomic factors leading to lifestyle and dietary issues, healthcare access problems, and potentially tumor biology.Recent findingsAlthough recent evidence suggests once access is equal, AA men have equal outcomes to Caucasian American (CA) men, differences in PCa incidence remain, and there is much to do to reverse disparities in mortality across the USA. A deeper understanding of these issues, both at the clinical and molecular level, can facilitate improved outcomes in the AA population. This review first discusses PCa oncogenesis in the context of its diverse hallmarks before benchmarking key molecular and genomic differences for PCa in AA men that have emerged in the recent literature. Studies have emphasized the importance of tumor microenvironment that contributes to both the unequal cancer burden and differences in clinical outcome between the races. Management of comorbidities like obesity, hypertension, and diabetes will provide an essential means of reducing prostate cancer incidence in AA men. Although requiring further AA specific research, several new treatment strategies such as immune checkpoint inhibitors used in combination PARP inhibitors and other emerging vaccines, including Sipuleucel‐T, have demonstrated some proven efficacy.ConclusionGenomic profiling to integrate clinical and genomic data for diagnosis, prognosis, and treatment will allow physicians to plan a “Precision Medicine” approach to AA men. There is a pressing need for further research for risk stratification, which may allow early identification of AA men with higher risk disease based on their unique clinical, genomic, and immunological profiles, which can then be mapped to appropriate clinical trials. Treatment options are outlined, with a concise description of recent work in AA specific populations, detailing several targeted therapies, including immunotherapy. Also, a summary of current clinical trials involving AA men is presented, and it is important that policies are adopted to ensure that AA men are actively recruited. Although it is encouraging that many of these explore the lifestyle and educational initiatives and therapeutic interventions, there is much still work to be done to reduce incidence and mortality in AA men and equalize current racial disparities.

Highlights

  • African Americans (AAs) in the United States have higher incidences and mortality for a number of cancers.[1]. Their lifetime risk of prostate cancer (PCa) is 1 in 6, with a lifetime risk of Prostate Cancer (PCa) specific mortality of 1 in 23.1 For non-Hispanic Whites their risk of PCa is lower with incidence of 1 in 8, and mortality of 1 in 42.1 The drivers of this epidemiological disparity in incidence and mortality are not clearly defined and complex, ranging from social networks causing lifestyle and dietary issues, healthcare access problems, comorbidities, and their influences on pelvic inflammation and tumor microenvironment, as well as tumor biology with associated differences in genomic, molecular, and immunological pathways.[1,2,3]

  • ETS FUSION POSITIVE TUMOURS: E26 Transformation Specific (ETS) transcription factor gene fusions are found in approximately half of prostate cancers,[87] the commonest of which is fusion of the androgen-responsive promoter Transmembrane Protease Serine 2 (TMPRSS2) with the ERG gene of the ETS family.[55]

  • Having outlined the fundamentals of oncogenesis for prostate cancer according to the “Hallmarks of Cancer”[16] in Table 1, studies highlighting specific differences for AA versus Caucasian American (CA) men will be discussed under the same headings

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Summary

| INTRODUCTION

African Americans (AAs) in the United States have higher incidences and mortality for a number of cancers.[1]. AA men have diverse and genetically heterogeneous ancestry, within Africa and Europe and the Americas, and so their molecular and immunological response to cancer as well as their tumor biology is likely to be diverse.[7] In addition to this recent epidemiological evidence, there have been reviews of the molecular and genomic aberrations in African American (AA) men, and detailed analyses of the molecular and genomic pathways of PCa for all ethnicities at times highlighting potential therapeutic targets.[8,9,10,11] Bhardwaj et al[8] outlined the molecular differences in PCa between AA and CA men, discussing genetic polymorphisms, gene mutations, epigenetic changes, and microRNAs, as well as comparative aberrations in the androgen receptor (AR), growth factor receptor (GFR), and inflammatory signaling pathways. This table aims to be used as a reference to benchmark molecular and genomic differences in AA men that have emerged in the recent literature, including differences in the tumor microenvironment and noncoding RNA. Enhanced activity has been demonstrated in 8% of localized PCa and 30% of cases with advanced disease, correlating with higher Gleason grade and poor survival

| SPECIFIC FINDINGS IN AFRICAN AMERICAN MEN
An epidemiological study of genetic Prostate cancer
11. Avelumab Plus 2nd-generation ADT in African American subjects with mCRPC
| CONCLUSION
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