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Medecine Sciences : M/S 2017Prostate cancer is a public health concern as it currently represents the most frequent malignancy in men in Europe. Progression of this hormone-dependent cancer is... (Review)
Review
Prostate cancer is a public health concern as it currently represents the most frequent malignancy in men in Europe. Progression of this hormone-dependent cancer is driven by androgens. Thus, the most common treatment for patients with advanced prostate cancer consists in an androgen ablation by castration therapy. However, the majority of patients relapses and develops a castration-resistant prostate cancer. This failure of androgen deprivation is related to the emergence of mutant and splice variants of the androgen receptor. Indeed, androgen receptor variants are ligand-independent, constitutively active and thus able to induce resistance to castration. This review focuses on AR variants signaling pathways and their role in resistance to castration and prostate cancer progression.
Topics: Castration; Disease Progression; Drug Resistance, Neoplasm; Humans; Male; Polymorphism, Genetic; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Receptors, Androgen; Signal Transduction
PubMed: 28945566
DOI: 10.1051/medsci/20173308021 -
Oncotarget Feb 2017Prostate-Tumor-Overexpressed-1 (PTOV1) is a conserved adaptor protein discovered as overexpressed in prostate cancer. Since its discovery, the number of binding partners... (Review)
Review
Prostate-Tumor-Overexpressed-1 (PTOV1) is a conserved adaptor protein discovered as overexpressed in prostate cancer. Since its discovery, the number of binding partners and associated cellular functions has increased and helped to identify PTOV1 as regulator of gene expression at transcription and translation levels. Its overexpression is associated with increased tumor grade and proliferation in prostate cancer and other neoplasms, including breast, ovarian, nasopharyngeal, squamous laryngeal, hepatocellular and urothelial carcinomas. An important contribution to higher levels of PTOV1 in prostate tumors is given by the frequent rate of gene amplifications, also found in other tumor types. The recent resolution of the structure by NMR of the PTOV domain in PTOV2, also identified as Arc92/ACID1/MED25, has helped to shed light on the functions of PTOV1 as a transcription factor. In parallel, by studying its interaction with RACK1, we have discovered PTOV1 action in promoting mRNAs translation. Here, we will focus on the role of PTOV1 in cancer, re-examine its pro-oncogenic effects and re-evaluate the most relevant interactions and evidences of its cellular functions. The data are used to formulate a model for the mechanisms of action of PTOV1 in line with its recently described activities and cellular pathways modulated in cancer.
Topics: Biomarkers, Tumor; Disease Progression; Gene Expression Regulation, Neoplastic; Humans; Male; Models, Genetic; Neoplasm Proteins; Prostatic Neoplasms; Protein Binding; Signal Transduction
PubMed: 28029646
DOI: 10.18632/oncotarget.14104 -
Urologia Internationalis 2012Despite recent improvements in detection and treatment, prostate cancer continues to be the most common malignancy and the second leading cause of cancer-related... (Review)
Review
Despite recent improvements in detection and treatment, prostate cancer continues to be the most common malignancy and the second leading cause of cancer-related mortality. Thus, although survival rate continues to improve, prostate cancer remains a compelling medical health problem. The major goal of prostate cancer imaging in the next decade will be more accurate disease characterization through the synthesis of anatomic, functional, and molecular imaging information in order to plan the most appropriate therapeutic strategy. No consensus exists regarding the use of imaging for evaluating primary prostate cancer. However, conventional and functional imaging are expanding their role in detection and local staging and, moreover, functional imaging is becoming of great importance in oncologic management and monitoring of therapy response. This review presents a multidisciplinary perspective on the role of conventional and functional imaging methods in prostate cancer staging.
Topics: Bone Neoplasms; Diagnostic Imaging; Diffusion Magnetic Resonance Imaging; Evidence-Based Medicine; Humans; Magnetic Resonance Spectroscopy; Male; Neoplasm Invasiveness; Neoplasm Staging; Positron-Emission Tomography; Predictive Value of Tests; Prognosis; Prostatic Neoplasms; Tomography, X-Ray Computed; Ultrasonography
PubMed: 22286304
DOI: 10.1159/000335205 -
Prostate Cancer and Prostatic Diseases Mar 2017Utilization of active surveillance (AS) for prostate cancer is increasing. Optimal selection criteria for this approach are undefined and questions remain on how best to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Utilization of active surveillance (AS) for prostate cancer is increasing. Optimal selection criteria for this approach are undefined and questions remain on how best to expand inclusion beyond typical men with very low- or low-risk disease. We sought to review the current experience with AS for men with intermediate-risk featuresMethods:PubMed was queried for all relevant original publications describing outcomes for men with prostate cancer managed with AS. Outcomes for patients with intermediate-risk features as defined by the primary investigators were studied when available and compared with similar risk men undergoing immediate treatment.
RESULTS
Cancer-specific survival for men managed initially with AS is similar to results published with immediate radical intervention. A total of five published AS series describe some outcomes for men with intermediate-risk features. Definitions of intermediate risk vary between studies. Men with Gleason 7 disease experience higher rates of clinical progression and are more likely to undergo treatment over time. Intermediate-risk men with Gleason 6 disease have similar outcomes to low-risk men. Men with Gleason 7 disease appear at higher risk for metastatic disease. Novel technologies including imaging and biomarkers may assist with patient selection and disease surveillance.
CONCLUSIONS
The contemporary experiences of AS for men with intermediate-risk features suggest that although these men are at higher risk for eventual prostate-directed treatment, some are not significantly compromising chances for longer-term cure. Men with more than minimal Gleason pattern 4, however, must be carefully selected and surveyed for early signs of progression and may be at increased risk of metastases. Incorporating information from advanced imaging and biomarker technology will likely individualize future treatment decisions while improving overall surveillance strategies.
Topics: Biomarkers, Tumor; Genetic Predisposition to Disease; Germ-Line Mutation; Humans; Male; Multimodal Imaging; Neoplasm Grading; Outcome Assessment, Health Care; Polymorphism, Single Nucleotide; Population Surveillance; Prostatic Neoplasms; Risk Assessment; Risk Factors
PubMed: 27801900
DOI: 10.1038/pcan.2016.51 -
Clinical Chemistry and Laboratory... Jun 2015The prostate-specific antigen (PSA) is currently the most used tumor marker in the early detection of the prostate cancer (PCa), despite its low specificity and low... (Review)
Review
The prostate-specific antigen (PSA) is currently the most used tumor marker in the early detection of the prostate cancer (PCa), despite its low specificity and low negative predictive value. New biomarkers, including urine prostate cancer gene 3 (PCA3) score, Prostate Health Index (PHI), and the four-kallikrein panel, have been investigated during recent years especially with the aim of detecting aggressive PCa. Results suggest the ability of these biomarkers to improve the specificity of PSA in the detection of PCa, although there are not enough results directly comparing these biomarkers to know their complementarity. The relationship with PCa aggressiveness seems to be confirmed for PHI and for the four-kallikrein panel, but not for PCA3 score. However, available results suggest that emerging biomarkers may be useful as part of a multivariable approach for the screening and prognosis of PCa. Nevertheless, larger prospective studies comparing these biomarkers are necessary to evaluate definitely their value in the management of early PCa.
Topics: Antigens, Neoplasm; Biomarkers, Tumor; Humans; Kallikreins; Male; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms
PubMed: 25581761
DOI: 10.1515/cclm-2014-0988 -
American Society of Clinical Oncology... May 2018The treatment landscape for metastatic castration-sensitive prostate cancer (mCSPC) has rapidly evolved over the past 5 years. Although androgen-deprivation therapy... (Review)
Review
The treatment landscape for metastatic castration-sensitive prostate cancer (mCSPC) has rapidly evolved over the past 5 years. Although androgen-deprivation therapy (ADT) is still the backbone of treatment, the addition of docetaxel or abiraterone acetate has improved outcomes for patients with mCSPC and become standard of care. With multiple treatment options available for patients with mCSPC, treatment selection to optimize patient outcomes has become increasingly difficult. Here, we review the clinical trials involving ADT plus docetaxel or abiraterone and provide clinicians with guidelines for treatment. Although surgery and/or radiation are standard of care for localized, intermediate- and high-risk prostate cancer, these treatments are not routinely used as part of initial treatment plans for patients with de novo mCSPC. Recent clinical data are challenging that dogma, and we review the literature on the addition of surgery and radiation to systemic therapy for mCSPC. Finally, the standard of care for oligometastatic prostate cancer (a subset of mCSPC with limited metastases) has not been established compared with that for some other cancers. We discuss the recent studies on metastasis-directed therapy for treatment of oligometastatic prostate cancer.
Topics: Clinical Trials as Topic; Combined Modality Therapy; Disease Management; Humans; Male; Neoplasm Metastasis; Neoplasm Staging; Patient Selection; Prostatic Neoplasms; Treatment Outcome
PubMed: 30231388
DOI: 10.1200/EDBK_200967 -
Trends in Endocrinology and Metabolism:... Dec 2011The androgen receptor (AR) is important for prostate cancer development and progression. Genome-wide mapping of AR binding sites in prostate cancer has found that the... (Review)
Review
The androgen receptor (AR) is important for prostate cancer development and progression. Genome-wide mapping of AR binding sites in prostate cancer has found that the majority of AR binding sites are located within non-promoter regions. These distal AR binding regions regulate AR target genes (e.g. UBE2C) involved in prostate cancer growth through chromatin looping. In addition to long-distance gene regulation, looping has been shown to induce spatial proximity of two genes otherwise located far away along the genomic sequence and the formation of double-strand DNA breaks, resulting in aberrant gene fusions (e.g. TMPRSS2-ERG) that also contribute to prostate tumorigenesis. Elucidating the mechanisms of AR-driven chromatin looping will increase our understanding of prostate carcinogenesis and may lead to the identification of new therapeutic targets.
Topics: Androgens; Animals; Carcinogens; Chromatin Assembly and Disassembly; Gene Fusion; Humans; Male; Molecular Targeted Therapy; Mutant Chimeric Proteins; Neoplasm Proteins; Prostatic Neoplasms; Receptors, Androgen; Signal Transduction
PubMed: 21889355
DOI: 10.1016/j.tem.2011.07.006 -
The Urologic Clinics of North America Nov 2017Androgen deprivation therapy (ADT) has been conventional treatment of newly diagnosed metastatic prostate cancer for more than 70 years. However, all patients... (Review)
Review
Androgen deprivation therapy (ADT) has been conventional treatment of newly diagnosed metastatic prostate cancer for more than 70 years. However, all patients eventually become castration-resistant and a significant proportion of life span is spent in the castration-resistant state. Prospective randomized control trials have incorporated early chemotherapy along with ADT based on the hypothesis that a significant level of resistance to ADT already exists in newly diagnosed metastatic prostate cancer and ADT exhibits synergistic antitumor activity with taxanes. We discuss the changing landscape of management of patients with newly diagnosed metastatic prostate cancer based on recently published landmark randomized trials.
Topics: Antineoplastic Agents, Hormonal; Humans; Male; Neoplasm Metastasis; Prostatic Neoplasms
PubMed: 29107277
DOI: 10.1016/j.ucl.2017.07.008 -
Annals of Oncology : Official Journal... Jun 2013In this meta-analysis, we evaluated associations between statins and recurrence-free survival (RFS) following treatment of localized prostate cancer, with attention to... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
In this meta-analysis, we evaluated associations between statins and recurrence-free survival (RFS) following treatment of localized prostate cancer, with attention to potential benefits among patients treated primarily with radiotherapy (RT) versus radical prostatectomy.
PATIENTS AND METHODS
We identified original studies examining the effect of statins on men who received definitive treatment of localized prostate cancer using a systematic search of the PubMed and EMBASE databases through August 2012. Our search yielded 17 eligible studies from 794 references; 13 studies with hazard ratios (HRs) for RFS were included in the formal meta-analysis.
RESULTS
Overall, statins did not affect RFS (HR 0.90, 95% CI 0.74-1.08). However, in RT patients (six studies), statins were associated with a statistically significant improvement in RFS (HR 0.68; 95% CI 0.49-0.93); this benefit was not observed in radical prostatectomy patients (seven studies). Sensitivity analyses suggested that primary treatment modality may impact the effect of statins on prostate cancer recurrence.
CONCLUSIONS
Our meta-analysis suggests a potentially beneficial effect of statins on prostate cancer patients treated with RT but not among radical prostatectomy patients. Although limited by the lack of randomized data, these results suggest that primary treatment modality should be considered in future studies examining associations between statins and oncologic outcomes.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Neoplasm Recurrence, Local; Prostatectomy; Prostatic Neoplasms
PubMed: 23508824
DOI: 10.1093/annonc/mdt077 -
The Lancet. Oncology Nov 2012Prostate cancer is generally multifocal and consists of a dominant focus-measured by tumour volume and deemed the index lesion-and one or more separate, secondary tumour... (Review)
Review
Prostate cancer is generally multifocal and consists of a dominant focus-measured by tumour volume and deemed the index lesion-and one or more separate, secondary tumour foci of smaller volume. Much laboratory and clinical evidence has shown that we need to rethink how we regard low-grade and low-volume prostate lesions. In this Personal View, we discuss why small, low-grade Gleason pattern prostate lesions, which are currently designated as prostate cancer, could be regarded as non-malignant. These lesions either do not meet the criteria of the hallmarks of cancer or robust evidence that they do so is absent, by contrast with large lesions with a high Gleason grade, which seem to cause most metastatic disease.
Topics: Apoptosis; Cell Communication; Humans; Laser Capture Microdissection; Male; Neoplasm Grading; Neoplasm Invasiveness; Neoplasm Metastasis; Neovascularization, Pathologic; Prostatic Neoplasms; Signal Transduction; Tumor Microenvironment
PubMed: 23117005
DOI: 10.1016/S1470-2045(12)70388-1