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International Journal of Molecular... Feb 2021Prostate cancer is the most frequent malignancy in the worldwide male population; it is also one of the most common among all the leading cancer-related death causes. In... (Review)
Review
Prostate cancer is the most frequent malignancy in the worldwide male population; it is also one of the most common among all the leading cancer-related death causes. In the last two decades, the therapeutic scenario of metastatic castration-resistant prostate cancer has been enriched by the use of chemotherapy and androgen receptor signaling inhibitors (ARSI) and, more recently, by immunotherapy and poly(ADP-ribose) polymerase (PARP) inhibitors. At the same time, several trials have shown the survival benefits related to the administration of novel ARSIs among patients with non-castration-resistant metastatic disease along with nonmetastatic castration-resistant cancer too. Consequently, the therapeutic course of this malignancy has been radically expanded, ensuring survival benefits never seen before. Among the more recently emerging agents, the so-called "antibody-drug conjugates" (ADCs) are noteworthy because of their clinical practice changing outcomes obtained in the management of other malignancies (including breast cancer). The ADCs are novel compounds consisting of cytotoxic agents (also known as the payload) linked to specific antibodies able to recognize antigens expressed over cancer cells' surfaces. As for prostate cancer, researchers are focusing on STEAP1, TROP2, PSMA, CD46 and B7-H3 as optimal antigens which may be targeted by ADCs. In this paper, we review the pivotal trials that have currently changed the therapeutic approach to prostate cancer, both in the nonmetastatic castration-resistant and metastatic settings. Therefore, we focus on recently published and ongoing trials designed to investigate the clinical activity of ADCs against prostate malignancy, characterizing these agents. Lastly, we briefly discuss some ADCs-related issues with corresponding strategies to overwhelm them, along with future perspectives for these promising novel compounds.
Topics: Animals; Antineoplastic Agents, Immunological; Biomarkers, Tumor; Clinical Trials as Topic; Disease Management; Disease Susceptibility; Humans; Immunoconjugates; Male; Molecular Targeted Therapy; Prognosis; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Standard of Care; Treatment Outcome
PubMed: 33557050
DOI: 10.3390/ijms22041551 -
Radiation Oncology (London, England) Mar 2021Due to improved imaging sensitivity, the term "oligometastatic" prostate cancer disease is diagnosed more often, leading to an increasing interest in metastasis-directed...
BACKGROUND
Due to improved imaging sensitivity, the term "oligometastatic" prostate cancer disease is diagnosed more often, leading to an increasing interest in metastasis-directed therapy (MDT). There are two types of radiation based MDT applied when treating oligometastatic disease: (1) stereotactic body radiation therapy (SBRT) generally used for bone metastases; or (2) SBRT for isolated nodal oligometastases combined with prophylactic elective nodal radiotherapy. This review aims to summarize current evidence data, which may shed light on the optimal management of this heterogeneous group of patients.
METHODS
A systematic review of the Medline database through PubMed was performed according to PRISMA guidelines. All relevant studies published up to November 2020 were identified and screened. Fifty-six titles were included. Besides outcome parameters, different prognostic and predictive factors were assessed, including site of metastases, time between primary treatment and MDT, use of systemic therapies, hormone sensitivity, as well as pattern of recurrence.
FINDINGS
Evidence consists largely of retrospective case series and no consistent precise definition of oligometastasis exists, however, most investigators seem to acknowledge the need to distinguish between patients presenting with what is frequently called "synchronous" versus "metachronous" oligometastatic disease. Available data on radiotherapy as MDT demonstrate high local control rates and a small but relevant proportion of patients without progressive disease after 2 years. This holds true for both hormone sensitive and castration resistant prostate cancer diseases. The use of Ga-PSMA PET/CT for staging increased dramatically. Radiation doses and field sizes varied considerably among the studies. The search for relevant prognostic and predictive factors is ongoing.
CONCLUSIONS
To our best knowledge this review on oligometastatic prostate cancer included the largest number of original articles. It demonstrates the therapeutic potential and challenges of MDT for oligometastatic prostate cancer. Prospective studies are under way and will provide further high-level evidence.
Topics: Bone Neoplasms; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Prostatic Neoplasms; Radiosurgery; Radiotherapy Dosage
PubMed: 33750437
DOI: 10.1186/s13014-021-01776-8 -
The Prostate Aug 2022Clinical genomic testing is becoming routine in prostate cancer, as biomarker-driven therapies such as poly-ADP ribose polymerase (PARP) inhibitors and anti-PD1... (Review)
Review
Clinical genomic testing is becoming routine in prostate cancer, as biomarker-driven therapies such as poly-ADP ribose polymerase (PARP) inhibitors and anti-PD1 immunotherapy are now approved for select men with castration-resistant prostate cancer harboring alterations in DNA repair genes. Challenges for precision medicine in prostate cancer include an overall low prevalence of actionable genomic alterations and a still limited understanding of the impact of tumor heterogeneity and co-occurring alterations on treatment response and outcomes across diverse patient populations. Expanded tissue-based technologies such as whole-genome sequencing, transcriptome analysis, epigenetic analysis, and single-cell RNA sequencing have not yet entered the clinical realm and could potentially improve upon our understanding of how molecular features of tumors, intratumoral heterogeneity, and the tumor microenvironment impact therapy response and resistance. Blood-based technologies including cell-free DNA, circulating tumor cells (CTCs), and extracellular vesicles (EVs) are less invasive molecular profiling resources that could also help capture intraindividual tumor heterogeneity and track dynamic changes that occur in the context of specific therapies. Furthermore, molecular imaging is an important biomarker tool within the framework of prostate cancer precision medicine with a capability to detect heterogeneity across metastases and potential therapeutic targets less invasively. Here, we review recent technological advances that may help promote the future implementation and value of precision oncology testing for patients with advanced prostate cancer.
Topics: Biomarkers; Genomics; Humans; Male; Neoplastic Cells, Circulating; Precision Medicine; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Tumor Microenvironment
PubMed: 35657153
DOI: 10.1002/pros.24354 -
TheScientificWorldJournal Apr 2011Prostate cancer continues to be a significant public health issue worldwide, particularly in countries where men have life expectancies long enough to clinically...
Prostate cancer continues to be a significant public health issue worldwide, particularly in countries where men have life expectancies long enough to clinically manifest the disease. In many countries, it remains one of the leading causes of cancer-related morbidity and mortality. Although significant progress has been made over the past few decades, many elements regarding the diagnosis and management of patients with prostate cancer remain enigmatic. In this Prostate Cancer special issue, our expert authors present and examine clinically relevant topics and look ahead to future research.
Topics: Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms
PubMed: 21479346
DOI: 10.1100/tsw.2011.79 -
Molecular Cancer Oct 2020The highly intra-tumoral heterogeneity and complex cell origination of prostate cancer greatly limits the utility of traditional bulk RNA sequencing in finding better...
BACKGROUND
The highly intra-tumoral heterogeneity and complex cell origination of prostate cancer greatly limits the utility of traditional bulk RNA sequencing in finding better biomarker for disease diagnosis and stratification. Tissue specimens based single-cell RNA sequencing holds great promise for identification of novel biomarkers. However, this technique has yet been used in the study of prostate cancer heterogeneity.
METHODS
Cell types and the corresponding marker genes were identified by single-cell RNA sequencing. Malignant states of different clusters were evaluated by copy number variation analysis and differentially expressed genes of pseudo-bulks sequencing. Diagnosis and stratification of prostate cancer was estimated by receiver operating characteristic curves of marker genes. Expression characteristics of marker genes were verified by immunostaining.
RESULTS
Fifteen cell groups including three luminal clusters with different expression profiles were identified in prostate cancer tissues. The luminal cluster with the highest copy number variation level and marker genes enriched in prostate cancer-related metabolic processes was considered the malignant cluster. This cluster contained a distinct subgroup with high expression level of prostate cancer biomarkers and a strong distinguishing ability of normal and cancerous prostates across different pathology grading. In addition, we identified another marker gene, Hepsin (HPN), with a 0.930 area under the curve score distinguishing normal tissue from prostate cancer lesion. This finding was further validated by immunostaining of HPN in prostate cancer tissue array.
CONCLUSION
Our findings provide a valuable resource for interpreting tumor heterogeneity in prostate cancer, and a novel candidate marker for prostate cancer management.
Topics: Biomarkers, Tumor; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Male; Prognosis; Prostatectomy; Prostatic Neoplasms; ROC Curve; Single-Cell Analysis; Survival Rate
PubMed: 33032611
DOI: 10.1186/s12943-020-01264-9 -
Cancer Aug 2021
Topics: COVID-19; Cancer Survivors; Delivery of Health Care; Humans; Male; Pandemics; Prostatic Neoplasms
PubMed: 33882148
DOI: 10.1002/cncr.33588 -
Ugeskrift For Laeger Apr 2023This review investigates prostate cancer which with approx. 4,500 new cases annually is the most frequent male cancer, and the incidence is expected to increase due to... (Review)
Review
This review investigates prostate cancer which with approx. 4,500 new cases annually is the most frequent male cancer, and the incidence is expected to increase due to demographic developments. Prostate cancer can have a natural history without progression to symptomatic or fatal disease, which is why overdiagnosis is one of the disease's biggest challenges. In contrast to potential curable localized clinically significant disease, this is not the case after metastasis. Fortunately, new treatments, and not least combinations thereof, have increased both lifespan and quality of life in these patients significantly.
Topics: Humans; Male; Quality of Life; Prostatic Neoplasms; Incidence
PubMed: 37057694
DOI: No ID Found -
Nutrients Dec 2022Vitamin E is a group of antioxidative tocopherols and tocotrienols that play a potential role in chemoprevention. Studies investigating the association between vitamin E... (Meta-Analysis)
Meta-Analysis
Vitamin E is a group of antioxidative tocopherols and tocotrienols that play a potential role in chemoprevention. Studies investigating the association between vitamin E and prostate cancer risk have been conflicting. We identified observational and interventional studies examining the association between vitamin E intake and prostate cancer risk from PubMed, EMBASE and the Cochrane Library. A random-effects model was used to perform a meta-analysis and estimate relative risks (RRs) and the corresponding 95% confidence intervals (CIs) of prostate cancer risk according to vitamin E intake. Subgroup analyses were conducted by study design, sample size, study population characteristics, geographical region, and dose of vitamin E intake. The association between dietary (RR = 0.97; 95% CI = 0.92-1.02) and supplemental (RR = 0.99; 95% CI = 0.94-1.04) vitamin E intake on prostate cancer risk was non-significant. In subgroup analyses, supplemental vitamin E was significantly associated with reduced prostate cancer risk in studies in Europe (RR = 0.81, 95% CI = 0.69-0.97). Overall, this meta-analysis demonstrates little evidence for a beneficial effect of vitamin E intake on prostate cancer risk but suggests that there may be some conditions in which supplements could confer a protective effect on prostate cancer risk.
Topics: Humans; Male; Antioxidants; Diet; Dietary Supplements; Prostatic Neoplasms; Risk; Vitamin E; Observational Studies as Topic
PubMed: 36615673
DOI: 10.3390/nu15010014 -
Journal of Nanobiotechnology Dec 2023Current diagnostic tools for prostate cancer (PCa) diagnosis and risk stratification are insufficient. The hidden onset and poor efficacy of traditional therapies... (Review)
Review
Current diagnostic tools for prostate cancer (PCa) diagnosis and risk stratification are insufficient. The hidden onset and poor efficacy of traditional therapies against metastatic PCa make this disease a heavy burden in global men's health. Prostate cancer-derived extracellular vesicles (PCDEVs) have garnered attention in recent years due to their important role in communications in tumor microenvironment. Recent advancements have demonstrated PCDEVs proteins play an important role in PCa invasion, progression, metastasis, therapeutic resistance, and immune escape. In this review, we briefly discuss the applications of sEV proteins in PCa diagnosis and prognosis in liquid biopsy, focus on the roles of the PCa-derived small EVs (sEVs) proteins in tumor microenvironment associated with cancer progression, and explore the therapeutic potential of sEV proteins applied for future metastatic PCa therapy.
Topics: Male; Humans; Prostatic Neoplasms; Prognosis; Extracellular Vesicles; Liquid Biopsy; Tumor Microenvironment
PubMed: 38093355
DOI: 10.1186/s12951-023-02219-0 -
International Journal of Molecular... Feb 2024Prostate cancer (PCa) represents the second most diagnosed tumor and the fifth most common cause of cancer death in men globally [...].
Prostate cancer (PCa) represents the second most diagnosed tumor and the fifth most common cause of cancer death in men globally [...].
Topics: Humans; Male; Prostatic Neoplasms
PubMed: 38396731
DOI: 10.3390/ijms25042054