-
Pathology, Research and Practice Aug 2023Globally, prostate cancer (PC) is leading cause of cancer-related mortality in men worldwide. Despite significant advances in the treatment and management of this... (Review)
Review
Globally, prostate cancer (PC) is leading cause of cancer-related mortality in men worldwide. Despite significant advances in the treatment and management of this disease, the cure rates for PC remains low, largely due to late detection. PC detection is mostly reliant on prostate-specific antigen (PSA) and digital rectal examination (DRE); however, due to the low positive predictive value of current diagnostics, there is an urgent need to identify new accurate biomarkers. Recent studies support the biological role of microRNAs (miRNAs) in the initiation and progression of PC, as well as their potential as novel biomarkers for patients' diagnosis, prognosis, and disease relapse. In the advanced stages, cancer-cell-derived small extracellular vesicles (SEVs) may constitute a significant part of circulating vesicles and cause detectable changes in the plasma vesicular miRNA profile. Recent computational model for the identification of miRNA biomarkers discussed. In addition, accumulating evidence indicates that miRNAs can be utilized to target PC cells. In this article, the current understanding of the role of microRNAs and exosomes in the pathogenesis and their significance in PC prognosis, early diagnosis, chemoresistance, and treatment are reviewed.
Topics: Male; Humans; MicroRNAs; Biomarkers, Tumor; Early Detection of Cancer; Neoplasm Recurrence, Local; Prostatic Neoplasms; Prognosis
PubMed: 37331185
DOI: 10.1016/j.prp.2023.154618 -
The Journal of Clinical Investigation Dec 2023Strategies for patient stratification and early intervention are required to improve clinical benefits for patients with prostate cancer. Here, we found that active DHEA...
Strategies for patient stratification and early intervention are required to improve clinical benefits for patients with prostate cancer. Here, we found that active DHEA utilization in the prostate gland correlated with tumor aggressiveness at early disease stages, and 3βHSD1 inhibitors were promising for early intervention. [3H]-labeled DHEA consumption was traced in fresh prostatic biopsies ex vivo. Active DHEA utilization was more frequently found in patients with metastatic disease or therapy-resistant disease. Genetic and transcriptomic features associated with the potency of prostatic DHEA utilization were analyzed to generate clinically accessible approaches for patient stratification. UBE3D, by regulating 3βHSD1 homeostasis, was discovered to be a regulator of patient metabolic heterogeneity. Equilin suppressed DHEA utilization and inhibited tumor growth as a potent 3βHSD1 antagonist, providing a promising strategy for the early treatment of aggressive prostate cancer. Overall, our findings indicate that patients with active prostatic DHEA utilization might benefit from 3βHSD1 inhibitors as early intervention.
Topics: Male; Humans; Prostate; Dehydroepiandrosterone; Prostatic Neoplasms
PubMed: 38099500
DOI: 10.1172/JCI171199 -
Life Sciences Jan 2024Data collected from large-scale studies has shown that the incidence of prostate cancer globally is on the rise, which could be attributed to an overall increase in... (Review)
Review
Data collected from large-scale studies has shown that the incidence of prostate cancer globally is on the rise, which could be attributed to an overall increase in lifespan. So, the question is how has modern science with all its new technologies and clinical breakthroughs mitigated or managed this disease? The answer is not a simple one as prostate cancer exhibits various subtypes, each with its unique characteristics or signatures which creates challenges in treatment. To understand the complexity of prostate cancer these signatures must be deciphered. Molecular studies of prostate cancer samples have identified certain genetic and epigenetic alterations, which are instrumental in tumorigenesis. Some of these candidates include the androgen receptor (AR), various oncogenes, tumor suppressor genes, and the tumor microenvironment, which serve as major drivers that lead to cancer progression. These aberrant genes and their products can give an insight into prostate cancer development and progression by acting as potent markers to guide future therapeutic approaches. Thus, understanding the complexity of prostate cancer is crucial for targeting specific markers and tailoring treatments accordingly.
Topics: Male; Humans; Prostatic Neoplasms; Receptors, Androgen; Gene Expression Regulation, Neoplastic; Orchiectomy; Disease Progression; Tumor Microenvironment
PubMed: 37979833
DOI: 10.1016/j.lfs.2023.122270 -
Biomedicine & Pharmacotherapy =... Dec 2023Androgen receptor (AR) signaling is essential in prostate cancer treatment. For many years, androgen deprivation therapy (ADT) has been primarily applied to manage... (Review)
Review
Androgen receptor (AR) signaling is essential in prostate cancer treatment. For many years, androgen deprivation therapy (ADT) has been primarily applied to manage advanced prostate cancer. However, most individuals with metastatic hormone-sensitive prostate cancer (mHSPC) administered ADT alone are at risk of developing metastatic castration-resistant prostate cancer (mCRPC) in less than two years. New approaches employing novel AR inhibitors (ARi) as intensified upfront systemic treatment in mHSPC have recently demonstrated substantial benefits in delaying disease progression and prolonging overall survival. Administration of novel ARi has become the new standard of care in mHSPC. The new landscape simultaneously makes treatment choice more challenging. This review provides comprehensive data on molecular structure, pharmaceutical properties, and efficacy and safety profiles reported by pivotal clinical trials. We also discuss future directions with ongoing Phase III trials of novel ARi in mHSPC. Considering these biological and clinical insights, this review aimed to provide a comprehensive understanding of differences in the development and applications of novel ARi for mHSPC, which may be helpful in designing strategies for first-line treatment choices.
Topics: Humans; Male; Androgen Receptor Antagonists; Hormones; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Receptors, Androgen; Treatment Outcome
PubMed: 37925933
DOI: 10.1016/j.biopha.2023.115806 -
The Proceedings of the Nutrition Society Sep 2023This review considers current evidence on physical activity and dietary behaviours in the context of prostate cancer prevention and survivorship outcomes. Prostate... (Review)
Review
This review considers current evidence on physical activity and dietary behaviours in the context of prostate cancer prevention and survivorship outcomes. Prostate cancer is the second most common cancer amongst men, with over 1⋅4 million newly diagnosed cases globally each year. Due to earlier detection via screening and advances in treatments, survival rates are amongst the highest of all cancer populations. However, hormone treatments (i.e. androgen deprivation therapy) can lead to undesirable body composition changes, increased fatigue and reduced health-related quality of life, which can impair the overall wellbeing of men living with and beyond prostate cancer. Existing research has only provided limited evidence that physical activity and nutrition can impact a man's risk of prostate cancer but cohort studies suggest they can influence survival outcomes after diagnosis. Additionally, data from observational and intervention studies suggest that habitual physical activity (or structured exercise) and healthy diets can help to ameliorate hormone-related treatment side-effects. Current physical activity guidelines state that prostate cancer patients should complete at least three sessions of moderate-intensity aerobic exercise per week, along with two resistance exercise sessions, but dietary guidelines for prostate cancer patients are less well defined. In conclusion, regular physical activity and nutritional interventions may improve survival outcomes and attenuate some adverse side-effects of hormone treatments in men with prostate cancer. However, further research is required to improve our understanding of the health impacts of physical activity (including structured exercise) and nutrition in relation to prostate cancer prevention and survivorship.
Topics: Male; Humans; Prostatic Neoplasms; Androgen Antagonists; Quality of Life; Exercise; Diet; Hormones
PubMed: 36606326
DOI: 10.1017/S0029665123000046 -
Investigative and Clinical Urology Jul 2023
Topics: Male; Humans; Prostatic Neoplasms; Prostate-Specific Antigen; Early Detection of Cancer; Mass Screening
PubMed: 37417555
DOI: 10.4111/icu.20230178 -
Discovery Medicine Oct 2023Synchronous or sequential development of multiple myeloma and prostate carcinoma is rare. It is not sure whether these two occur independently or if one influences the... (Review)
Review
Synchronous or sequential development of multiple myeloma and prostate carcinoma is rare. It is not sure whether these two occur independently or if one influences the development of the other. We reviewed the cases published in the English literature; eight cases of myeloma developing after diagnosis and treatment for prostate carcinoma, five cases of simultaneous occurrence of myeloma and prostate carcinoma, and five cases where the patient with multiple myeloma later developed prostate carcinoma were found. This short review attempts to analyze the occurrence of these two diseases in the same patient and dissect whether there is a close association or it is just a mere coincidence.
Topics: Male; Humans; Multiple Myeloma; Prostate; Prostatic Neoplasms; Carcinoma
PubMed: 37811608
DOI: 10.24976/Discov.Med.202335178.65 -
Clinical Nuclear Medicine Jan 2024Diagnosis and treatment of prostate cancer are complex and very challenging, being a major health care burden. The efficacy of radioligand therapy with prostate-specific... (Review)
Review
Diagnosis and treatment of prostate cancer are complex and very challenging, being a major health care burden. The efficacy of radioligand therapy with prostate-specific membrane antigen agents has been proven beneficial in certain clinical indications. In this review, we describe management of prostate cancer patients according to current guidelines, especially focusing on the available clinical evidence for prostate-specific membrane antigen radioligand therapy.
Topics: Male; Humans; Prostate-Specific Antigen; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant
PubMed: 37882758
DOI: 10.1097/RLU.0000000000004919 -
Nature Reviews. Urology May 2024Black men with prostate cancer have historically had worse outcomes than white men with prostate cancer. The causes of this disparity in outcomes are multi-factorial,... (Review)
Review
Black men with prostate cancer have historically had worse outcomes than white men with prostate cancer. The causes of this disparity in outcomes are multi-factorial, but a potential basis is that prostate cancers in Black men are biologically distinct from prostate cancers in white men. Evidence suggests that genetic and ancestral factors, molecular pathways involving androgen and non-androgen receptor signalling, inflammation, epigenetics, the tumour microenvironment and tumour metabolism are contributing factors to the racial disparities observed. Key genetic and molecular pathways linked to prostate cancer risk and aggressiveness have potential clinical relevance. Describing biological drivers of prostate cancer disparities could inform efforts to improve outcomes for Black men with prostate cancer.
Topics: Male; Humans; Prostatic Neoplasms; Black or African American; Health Status Disparities
PubMed: 37964070
DOI: 10.1038/s41585-023-00828-w -
International Journal of Urology :... Jun 2024Liquid biopsy has emerged as a valuable and minimally invasive tool for real-time detection of clinically actionable abnormalities across various cancer types. Its... (Review)
Review
Liquid biopsy has emerged as a valuable and minimally invasive tool for real-time detection of clinically actionable abnormalities across various cancer types. Its applicability is particularly compelling in the realm of prostate cancer, where novel therapeutic agents, including those targeting DNA repair systems, are under development. Despite these advancements, challenges persist in effectively screening for prostate cancer, enhancing risk stratification, and determining optimal approaches for treating advanced disease. Consequently, there is a pressing need for improved biomarkers to aid clinicians in decision-making within these contexts. Cell-free DNA and extracellular vesicle analysis have demonstrated promise in diagnosis, prognostication, assessment of treatment responses, and identification of emerging mechanisms of resistance. Nevertheless, obstacles must be addressed before liquid biopsies can be integrated into routine clinical practice. These challenges encompass preanalytical considerations such as sample collection and storage, methods of extracellular vesicle isolation and enrichment, and the need for enhanced interpretation of generated sequencing data. This review provides a comprehensive overview of current clinical opportunities in managing prostate cancer through blood-based liquid biopsy, highlighting the progress made, and acknowledging the challenges that remain. Additionally, we discuss the next steps required for the effective implementation of liquid biopsies in guiding personalized treatment strategies for prostate cancer.
Topics: Humans; Liquid Biopsy; Prostatic Neoplasms; Male; Extracellular Vesicles; Biomarkers, Tumor; Precision Medicine; Prognosis; Cell-Free Nucleic Acids; Early Detection of Cancer; Prostate
PubMed: 38551314
DOI: 10.1111/iju.15441