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1.
Targeting autophagy in prostate cancer: preclinical and clinical evidence for therapeutic response.
Ashrafizadeh, M, Paskeh, MDA, Mirzaei, S, Gholami, MH, Zarrabi, A, Hashemi, F, Hushmandi, K, Hashemi, M, Nabavi, N, Crea, F, et al
Journal of experimental & clinical cancer research : CR. 2022;(1):105
Abstract
Prostate cancer is a leading cause of death worldwide and new estimates revealed prostate cancer as the leading cause of death in men in 2021. Therefore, new strategies are pertinent in the treatment of this malignant disease. Macroautophagy/autophagy is a "self-degradation" mechanism capable of facilitating the turnover of long-lived and toxic macromolecules and organelles. Recently, attention has been drawn towards the role of autophagy in cancer and how its modulation provides effective cancer therapy. In the present review, we provide a mechanistic discussion of autophagy in prostate cancer. Autophagy can promote/inhibit proliferation and survival of prostate cancer cells. Besides, metastasis of prostate cancer cells is affected (via induction and inhibition) by autophagy. Autophagy can affect the response of prostate cancer cells to therapy such as chemotherapy and radiotherapy, given the close association between autophagy and apoptosis. Increasing evidence has demonstrated that upstream mediators such as AMPK, non-coding RNAs, KLF5, MTOR and others regulate autophagy in prostate cancer. Anti-tumor compounds, for instance phytochemicals, dually inhibit or induce autophagy in prostate cancer therapy. For improving prostate cancer therapy, nanotherapeutics such as chitosan nanoparticles have been developed. With respect to the context-dependent role of autophagy in prostate cancer, genetic tools such as siRNA and CRISPR-Cas9 can be utilized for targeting autophagic genes. Finally, these findings can be translated into preclinical and clinical studies to improve survival and prognosis of prostate cancer patients.
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2.
Prostate-specific Membrane Antigen PET in Prostate Cancer.
Lawhn-Heath, C, Salavati, A, Behr, SC, Rowe, SP, Calais, J, Fendler, WP, Eiber, M, Emmett, L, Hofman, MS, Hope, TA
Radiology. 2021;(2):248-260
Abstract
Prostate-specific membrane antigen (PSMA)-targeted radiopharmaceuticals are playing a large role at the time of initial staging and biochemical recurrence for localizing prostate cancer, as well as in other emerging clinical settings. PSMA PET has demonstrated increased detection rate compared with conventional imaging and has been shown to change management plans in a substantial percentage of cases. The aims of this narrative review are to highlight the development and clinical impact of PSMA PET radiopharmaceuticals, to compare PSMA to other agents such as fluorine 18 fluciclovine and carbon 11 choline, and to highlight some of the individual PSMA PET agents that have contributed to the advancement of prostate cancer imaging.
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3.
Public interest in dietary supplements for prostate cancer prevention.
Patel, DN, Kuhlmann, P, Lin, PH, Freedland, SJ
Prostate cancer and prostatic diseases. 2021;(1):58-60
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4.
Targeted nanomedicine modalities for prostate cancer treatment.
Cohen, L, Livney, YD, Assaraf, YG
Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy. 2021;:100762
Abstract
Prostate cancer (PC) is the second most common cause of death amongst men in the USA. Therapy of PC has been transformed in the past decade by introducing novel therapeutics, advanced functional imaging and diagnostic approaches, next generation sequencing, as well as improved application of existing therapies in localized PC. Treatment of PC at the different stages of the disease may include surgery, androgen deprivation therapy (ADT), chemotherapy and radiation therapy. However, although ADT has proven efficacious in PC treatment, its effectiveness may be temporary, as these tumors frequently develop molecular mechanisms of therapy resistance, which allow them to survive and proliferate even under conditions of testosterone deprivation, inhibition of androgen receptor signaling, or cytotoxic drug treatment. Importantly, ADT was found to induce key alterations which frequently result in the formation of metastatic tumors displaying a therapy refractory phenotype. Hence, to overcome these serious therapeutic impediments, novel PC cell-targeted therapeutic strategies are being developed. These include diverse platforms enabling specific enhanced antitumor drug uptake and increased intracellular accumulation. Studies have shown that these novel treatment modalities lead to enhanced antitumor activity and diminished systemic toxicity due to the use of selective targeting and decreased drug doses. The underlying mechanism of targeting and internalization is based upon the interaction between a selective ligand, conjugated to a drug-loaded nanoparticle or directly to an anti-cancer drug, and a specific plasma membrane biomarker, uniquely overexpressed on the surface of PC cells. Another targeted therapeutic approach is the delivery of unique anti-oncogenic signaling pathway-based therapeutic drugs, which are selectively cytotoxic to PC cells. The current paper reviews PC targeted modalities reported in the past 6 years, and discusses both the advantages and limitations of the various targeted treatment strategies.
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5.
Long non-coding RNA regulating androgen receptor signaling in breast and prostate cancer.
Kumar, S, Prajapati, KS, Singh, AK, Kushwaha, PP, Shuaib, M, Gupta, S
Cancer letters. 2021;:15-22
Abstract
The human genome transcribe an array of RNAs that do not encode proteins and may act as mediators in the regulation of gene expression. Long non-coding RNAs (lncRNAs) are a group of non-coding RNAs consisting of more than 200 nucleotides of RNA transcripts that play important role in tumor development. Numerous lncRNAs have been characterized as functional transcripts associated with several biological processes and pathologic stages. Although the biological function and molecular mechanisms of lncRNAs remains to be explored, recent studies demonstrate aberrant expression of several lncRNAs linked with various human cancers. The present review summarizes the current knowledge of lncRNA expression patterns and mechanisms that contribute to carcinogenesis. In particular, we focus on lncRNAs regulating androgen receptor signaling pathways in prostate and breast cancer subtype having prognostic and therapeutic implications.
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6.
Using Exercise and Nutrition to Alter Fat and Lean Mass in Men with Prostate Cancer Receiving Androgen Deprivation Therapy: A Narrative Review.
Wilson, RL, Taaffe, DR, Newton, RU, Hart, NH, Lyons-Wall, P, Galvão, DA
Nutrients. 2021;(5)
Abstract
Fat mass (FM) gain and lean mass (LM) loss are common side effects for patients with prostate cancer receiving androgen deprivation therapy (ADT). Excess FM has been associated with an increased risk of developing obesity-related comorbidities, exacerbating prostate cancer progression, and all-cause and cancer-specific mortality. LM is the predominant contributor to resting metabolic rate, with any loss impacting long-term weight management as well as physical function. Therefore, reducing FM and preserving LM may improve patient-reported outcomes, risk of disease progression, and ameliorate comorbidity development. In ADT-treated patients, exercise and nutrition programs can lead to improvements in quality of life and physical function; however, effects on body composition have been variable. The aim of this review was to provide a descriptive overview and critical appraisal of exercise and nutrition-based interventions in prostate cancer patients on ADT and their effect on FM and LM. Our findings are that FM gain and LM loss are side effects of ADT that could be reduced, prevented, or even reversed with the implementation of a combined exercise and nutrition program. However, the most effective combination of specific exercise and nutrition prescriptions are yet to be determined, and thus should be a focus for future studies.
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7.
Cardiorespiratory fitness is not associated with reduced risk of prostate cancer: A cohort study and review of the literature.
Kunutsor, SK, Voutilainen, A, Laukkanen, JA
European journal of clinical investigation. 2021;(8):e13545
Abstract
BACKGROUND Cardiorespiratory fitness (CRF) has a strong inverse relationship with several chronic disease outcomes, including some cancers. The association between CRF and prostate cancer is controversial. We aimed to assess the prospective association of CRF with prostate cancer risk using a cohort study and review of the literature. MATERIAL AND METHODS Cardiorespiratory fitness was assessed using a respiratory gas exchange analyser during exercise testing in 2204 cancer-free middle-aged men. Hazard ratios (HRs) with 95% confidence interval (CIs) were estimated. We corrected for within-person variability in CRF levels using repeat measurements. RESULTS During a median follow-up of 24.9 years, 216 prostate cancer cases occurred. The age-adjusted regression dilution ratio of CRF was 0.58 (95% CI: 0.53-0.64). The HR (95% CI) of prostate cancer per 1 standard deviation increase in CRF in age-adjusted analysis was 1.10 (0.95-1.27). The association remained consistent after further adjustment for several risk factors (HR 1.13; 95% CI 0.96-1.33). The corresponding adjusted HRs were 1.24 (95% CI: 0.87-1.77) and 1.28 (95% CI: 0.87-1.88), respectively, when comparing the extreme tertiles of CRF levels. Previous studies mostly reported no evidence of an association or an increased risk of prostate cancer in relation to high CRF. Studies reporting positive associations had short-term follow-up durations (<10 years). CONCLUSIONS Primary data and a review of previous studies suggest that elevated CRF is not associated with reduced prostate cancer risk. Previous findings of significant evidence of associations could be attributed to increased screening and detection as well as reverse causation bias.
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8.
The Crosstalk between Prostate Cancer and Microbiota Inflammation: Nutraceutical Products Are Useful to Balance This Interplay?
Crocetto, F, Boccellino, M, Barone, B, Di Zazzo, E, Sciarra, A, Galasso, G, Settembre, G, Quagliuolo, L, Imbimbo, C, Boffo, S, et al
Nutrients. 2020;(9)
Abstract
The human microbiota shows pivotal roles in urologic health and disease. Emerging studies indicate that gut and urinary microbiomes can impact several urological diseases, both benignant and malignant, acting particularly on prostate inflammation and prostate cancer. Indeed, the microbiota exerts its influence on prostate cancer initiation and/or progression mechanisms through the regulation of chronic inflammation, apoptotic processes, cytokines, and hormonal production in response to different pathogenic noxae. Additionally, therapies' and drugs' responses are influenced in their efficacy and tolerability by microbiota composition. Due to this complex potential interconnection between prostate cancer and microbiota, exploration and understanding of the involved relationships is pivotal to evaluate a potential therapeutic application in clinical practice. Several natural compounds, moreover, seem to have relevant effects, directly or mediated by microbiota, on urologic health, posing the human microbiota at the crossroad between prostatic inflammation and prostate cancer development. Here, we aim to analyze the most recent evidence regarding the possible crosstalk between prostate, microbiome, and inflammation.
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9.
Drug-Drug Interactions in Prostate Cancer Treatment.
Hebenstreit, D, Pichler, R, Heidegger, I
Clinical genitourinary cancer. 2020;(2):e71-e82
Abstract
Polypharmacy is associated with an increased risk of drug-drug interactions (DDIs), which can cause serious and debilitating drug-induced adverse events. With a steadily aging population and associated increasing multimorbidity and polypharmacy, the potential for DDIs becomes considerably important. Prostate cancer (PCa) is the most common cancer in men and occurs mostly in elderly men in the Western world. Therefore, the aim of this review is to give an overview of DDIs in PCa therapy to better understand pharmacodynamic and pharm kinetic side effects as well as their interactions with other medications. Last, we explore potential future strategies, which might help to optimize treatment and reduce adverse events patients with polypharmacy and PCa.
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10.
Systemic Treatment of Bone Disease in Metastatic Urinary Malignancies.
Patel, SH, Panian, J, Bree, K, Derweesh, I, Millard, F, Randall, J, Mckay, R
European urology focus. 2020;(1):17-25
Abstract
CONTEXT Bone metastasis is a common site of metastatic disease in patients with genitourinary malignancies. Given that the presence of bone metastasis decreases survival and has a negative impact on quality of life impact, it is critical to optimize management of this patient population. OBJECTIVE To systematically review literature on the systemic treatment of bone metastasis in prostate cancer, renal cell carcinoma, urothelial carcinoma, and germ cell tumors. EVIDENCE ACQUISITION We performed a nonsystematic critical review of PubMed/Medline, clinicaltrials.gov, and the Cochrane Library from January 2001 to February 2019. Identified reports were reviewed according to the Consolidated Standards of Reporting Trials, and selected based on reporting skeletal related events and symptomatic skeletal events for patients with urologic malignancies. EVIDENCE SYNTHESIS Skeletal metastases occur frequently in genitourinary malignancies, at rates around 80% for patients with metastatic prostate cancer and 30% for patients with metastatic renal cell and urothelial carcinoma, and are uncommon in patients with germ cell tumors. Skeletal related events and symptomatic skeletal events can occur in these patients. Optimization of bone health involves dietary and lifestyle modifications, and use of osteoclast-targeted agents in select individuals. Additionally, disease-modifying agents, such as radiopharmaceutical, immunotherapy, and cMET inhibitors, which have activity in the bone, have improved outcomes for patients, including skeletal-related events and symptomatic skeletal events. CONCLUSIONS While the presence of bone metastases is associated with increased mortality and worse outcomes in patients with genitourinary malignancies, strategies have been developed to improve quality of life and survival for patients with skeletal metastases. Future studies investigating novel therapeutic options and bone supporting agents are warranted to target this patient population. PATIENT SUMMARY In this report, we reviewed the current literature and recent clinical trials involving treatment of bone metastases in urinary cancers. The use of bone-targeting agents can improve outcomes for patients, and additional lifestyle modification can optimize bone health in this population.