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The New England Journal of Medicine Jul 2023
Topics: Male; Humans; Early Detection of Cancer; Prostatic Neoplasms; Prostate-Specific Antigen
PubMed: 37407014
DOI: 10.1056/NEJMc2305651 -
Oncogene May 2024Prostate cancer (CaP) remains the second leading cause of cancer deaths in western men. CaP mortality results from diverse molecular mechanisms that mediate resistance... (Review)
Review
Prostate cancer (CaP) remains the second leading cause of cancer deaths in western men. CaP mortality results from diverse molecular mechanisms that mediate resistance to the standard of care treatments for metastatic disease. Recently, alternative splicing has been recognized as a hallmark of CaP aggressiveness. Alternative splicing events cause treatment resistance and aggressive CaP behavior and are determinants of the emergence of the two major types of late-stage treatment-resistant CaP, namely castration-resistant CaP (CRPC) and neuroendocrine CaP (NEPC). Here, we review recent multi-omics data that are uncovering the complicated landscape of alternative splicing events during CaP progression and the impact that different gene transcript isoforms can have on CaP cell biology and behavior. We discuss renewed insights in the molecular machinery by which alternative splicing occurs and contributes to the failure of systemic CaP therapies. The potential for alternative splicing events to serve as diagnostic markers and/or therapeutic targets is explored. We conclude by considering current challenges and promises associated with splicing-modulating therapies, and their potential for clinical translation into CaP patient care.
Topics: Humans; Alternative Splicing; Male; Drug Resistance, Neoplasm; Disease Progression; Prostatic Neoplasms, Castration-Resistant; Prostatic Neoplasms; Gene Expression Regulation, Neoplastic; Animals
PubMed: 38658776
DOI: 10.1038/s41388-024-03036-x -
Current Oncology (Toronto, Ont.) Aug 2023Theranostics (therapy + diagnosis) targeting prostate-specific membrane antigen (PSMA) is an emerging therapeutic modality that could alter treatment strategies for... (Review)
Review
Theranostics (therapy + diagnosis) targeting prostate-specific membrane antigen (PSMA) is an emerging therapeutic modality that could alter treatment strategies for prostate cancer. Although PSMA-targeted radioligand therapy (PSMA-RLT) has a highly therapeutic effect on PSMA-positive tumor tissue, the efficacy of PSMA-RLT depends on PSMA expression. Moreover, predictors of treatment response other than PSMA expression are under investigation. Therefore, the optimal patient population for PSMA-RLT remains unclear. This review provides an overview of the current status of theranostics for prostate cancer, focusing on PSMA ligands. In addition, we summarize various findings regarding the efficacy and problems of PSMA-RLT and discuss the optimal patient for PSMA-RLT.
Topics: Humans; Male; Molecular Imaging; Prostatic Neoplasms
PubMed: 37623010
DOI: 10.3390/curroncol30080529 -
The Journal of Urology Oct 2023
Topics: Male; Humans; Urology; Prostatic Neoplasms; Medical Oncology; Urologic Neoplasms
PubMed: 37503946
DOI: 10.1097/JU.0000000000003633 -
The Journal of Urology Sep 2023
Topics: Male; Humans; Urology; Prostatic Neoplasms; Medical Oncology; Urologic Neoplasms
PubMed: 37334535
DOI: 10.1097/JU.0000000000003587 -
The Journal of Urology Nov 2023
Topics: Male; Humans; Urology; Prostatic Neoplasms; Medical Oncology; Urologic Neoplasms
PubMed: 37622534
DOI: 10.1097/JU.0000000000003675 -
Prostate Cancer and Prostatic Diseases Jun 2024Prostate cancer (PCa), one of the most prevalent malignancies affecting men, significantly contributes to increased mortality rates worldwide. While the causative death... (Review)
Review
BACKGROUND
Prostate cancer (PCa), one of the most prevalent malignancies affecting men, significantly contributes to increased mortality rates worldwide. While the causative death is due to advanced metastatic disease, this occurrence disproportionately impacts men of African descent compared to men of European descent. In this review, we describe potential mechanisms underlying PCa metastases disparities and current treatments for metastatic disease among these populations, differences in treatment outcomes, and survival rates, in hopes of highlighting a need to address disparities in PCa metastases.
METHODS
We reviewed existing literature using databases such as PubMed, Google Scholar, and Science Direct using the following keywords: "prostate cancer metastases", "metastatic prostate cancer disparity", "metastatic prostate cancer diagnosis and treatment", "prostate cancer genetic differences and mechanisms", "genetic differences and prostate tumor microenvironment", and "men of African descent and access to clinical treatments". The inclusion criteria for literature usage were original research articles and review articles.
RESULTS
Studies indicate unique genetic signatures and molecular mechanisms such as Epithelial-Mesenchymal Transition (EMT), inflammation, and growth hormone signaling involved in metastatic PCa disparities. Clinical studies also demonstrate differences in treatment outcomes that are race-specific, for example, patients of African descent have a better response to enzalutamide and immunotherapy yet have less access to these drugs as compared to patients of European descent.
CONCLUSIONS
Growing evidence suggests a connection between a patient's genetic profile, the prostate tumor microenvironment, and social determinants of health that contribute to the aggressiveness of metastatic disease and treatment outcomes. With several potential pathways highlighted, the limitations in current diagnostic and therapeutic applications that target disparity in PCa metastases warrant rigorous research attention.
Topics: Humans; Prostatic Neoplasms; Male; Neoplasm Metastasis; Tumor Microenvironment; Healthcare Disparities; Health Status Disparities; Epithelial-Mesenchymal Transition
PubMed: 37046071
DOI: 10.1038/s41391-023-00667-1 -
Genome Medicine Oct 2023Prostate cancer (PrCa) genomic heterogeneity causes resistance to therapies such as androgen deprivation. Such heterogeneity can be deciphered in the context of...
BACKGROUND
Prostate cancer (PrCa) genomic heterogeneity causes resistance to therapies such as androgen deprivation. Such heterogeneity can be deciphered in the context of evolutionary principles, but current clinical trials do not include evolution as an essential feature. Whether or not analysis of genomic data in an evolutionary context in primary prostate cancer can provide unique added value in the research and clinical domains remains an open question.
METHODS
We used novel processing techniques to obtain whole genome data together with 3D anatomic and histomorphologic analysis in two men (GP5 and GP12) with high-risk PrCa undergoing radical prostatectomy. A total of 22 whole genome-sequenced sites (16 primary cancer foci and 6 lymph node metastatic) were analyzed using evolutionary reconstruction tools and spatio-evolutionary models. Probability models were used to trace spatial and chronological origins of the primary tumor and metastases, chart their genetic drivers, and distinguish metastatic and non-metastatic subclones.
RESULTS
In patient GP5, CDK12 inactivation was among the first mutations, leading to a PrCa tandem duplicator phenotype and initiating the cancer around age 50, followed by rapid cancer evolution after age 57, and metastasis around age 59, 5 years prior to prostatectomy. In patient GP12, accelerated cancer progression was detected after age 54, and metastasis occurred around age 56, 3 years prior to prostatectomy. Multiple metastasis-originating events were identified in each patient and tracked anatomically. Metastasis from prostate to lymph nodes occurred strictly ipsilaterally in all 12 detected events. In this pilot, metastatic subclone content analysis appears to substantially enhance the identification of key drivers. Evolutionary analysis' potential impact on therapy selection appears positive in these pilot cases.
CONCLUSIONS
PrCa evolutionary analysis allows tracking of anatomic site of origin, timing of cancer origin and spread, and distinction of metastatic-capable from non-metastatic subclones. This enables better identification of actionable targets for therapy. If extended to larger cohorts, it appears likely that similar analyses could add substantial biological insight and clinically relevant value.
Topics: Male; Humans; Middle Aged; Prostatic Neoplasms; Androgen Antagonists; Precision Medicine; Prostatectomy; Oncogenes
PubMed: 37828555
DOI: 10.1186/s13073-023-01242-y -
Current Cardiology Reports Aug 2023Prostate cancer (PCa) is amongst the most common cancers in men worldwide. Cardiovascular (CV) risk factors and CV disease (CVD) are common comorbidities in this patient... (Review)
Review
PURPOSE OF REVIEW
Prostate cancer (PCa) is amongst the most common cancers in men worldwide. Cardiovascular (CV) risk factors and CV disease (CVD) are common comorbidities in this patient population, posing a challenge for PCa-directed therapies which can cause or worsen CVRFs and CVDs. Herein, we summarize the approaches to prevent and manage CVD in patients with PCa receiving therapy.
RECENT FINDINGS
While patients with locally advanced and metastatic PCa benefit from hormonal therapy, these treatments can potentially cause CV toxicity. Androgen receptor targeting therapies, such as androgen deprivation therapy (ADT), can induce metabolic changes and directly impact cardiovascular function, thereby reducing cardiorespiratory fitness and increasing CV mortality. Moreover, more than half of the PCa patients have poorly controlled CV risk factors at baseline. Hence, there is an urgent need to address gaps in preventing and managing CVD in PCa patients. Screening and optimizing CV risk factors and CVD in patients undergoing ADT are essential to reduce CV mortality, the leading non-cancer cause of death in PCa survivors. The risk of CV morbidity and mortality can be further mitigated by considering the patient's cardiovascular risk profile when deciding the choice and duration of ADT. A multidisciplinary team-based approach is crucial to achieve the best outcomes for PCa patients undergoing therapy.
Topics: Male; Humans; Prostatic Neoplasms; Cardiovascular Diseases; Androgen Antagonists; Antineoplastic Agents, Hormonal; Comorbidity
PubMed: 37490155
DOI: 10.1007/s11886-023-01909-3 -
The Canadian Journal of Urology Apr 2024
Topics: Male; Humans; Prostatic Neoplasms; Gallium Isotopes; Positron-Emission Tomography; Neoplasm Staging
PubMed: 38642457
DOI: No ID Found