Ever since the discovery of recurrent gene fusions in prostate cancer in 20053, several prostate cancer specific molecular aberrations have been identified and are potentially targetable with specific inhibitors (Figure 1). Despite the high prevalence, the clinical utility and association of these markers with disease progression has not been firmly established. It may be due to the fact that the estimates on the prevalence of these molecular markers and clinical correlation analyses were based on conventional approaches which routinely uses tumor samples from dominant or index nodule. Given the multifocal tumor and morphological heterogeneity we hypothesize that each tumor foci may be genetically distinct (molecular heterogeneity) and may
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SPECIFIC AIMS: AA men have a nearly two-fold higher prostate cancer mortality rate than EA men. Clinical studies show similar outcomes in prostate cancer when pathological stage is organ-confined, However, AA men often present with higher PSA levels, higher grade disease will suffer worse disease outcomes than EA when disease is locally advanced or metastatic30. The reasons for existing disparities are not well understood, but are believed to be multi-factorial. Potential contributors include socioeconomic factors that hinder accessibility to prostate cancer screening and appropriate medical treatment, and racial differences in cancer biology. By recognizing that there are potential racial differences in the biology of prostate cancer, it is an urgent unmet clinical need for the development of novel markers for screening, detection, and treatment of prostate cancer in AA men. Our proposal to screen for the known prostate molecular markers in AA men, discovery of new markers of disease and understand the genetic heterogeneity of prostate cancer will allow us to learn the underlying genetic differences of AA PCa compared with EA PCa.
The important questions that we propose to address in this project are to 1) Estimate the prevalence of known prostate molecular markers in AA PCa by an unbiased screening of whole-mount prostatectomy specimens rather than testing selected samples of tumor from dominant/index nodule- [Specific Aim 1] 2) To discover new molecular biomarker in AA PCa using next generation sequencing of ETS fusion negative AA PCa [Specific Aim
SPECIFIC AIMS: AA men have a nearly two-fold higher prostate cancer mortality rate than EA men. Clinical studies show similar outcomes in prostate cancer when pathological stage is organ-confined, However, AA men often present with higher PSA levels, higher grade disease will suffer worse disease outcomes than EA when disease is locally advanced or metastatic30. The reasons for existing disparities are not well understood, but are believed to be multi-factorial. Potential contributors include socioeconomic factors that hinder accessibility to prostate cancer screening and appropriate medical treatment, and racial differences in cancer biology. By recognizing that there are potential racial differences in the biology of prostate cancer, it is an urgent unmet clinical need for the development of novel markers for screening, detection, and treatment of prostate cancer in AA men. Our proposal to screen for the known prostate molecular markers in AA men, discovery of new markers of disease and understand the genetic heterogeneity of prostate cancer will allow us to learn the underlying genetic differences of AA PCa compared with EA PCa.
The important questions that we propose to address in this project are to 1) Estimate the prevalence of known prostate molecular markers in AA PCa by an unbiased screening of whole-mount prostatectomy specimens rather than testing selected samples of tumor from dominant/index nodule- [Specific Aim 1] 2) To discover new molecular biomarker in AA PCa using next generation sequencing of ETS fusion negative AA PCa [Specific Aim