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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.
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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4.
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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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.
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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8.
Advances of Zinc Signaling Studies in Prostate Cancer.
Li, D, Stovall, DB, Wang, W, Sui, G
International journal of molecular sciences. 2020;(2)
Abstract
Prostate cancer (PCa) is one of the most common cancers and the second leading cause of cancer-related death among men worldwide. Despite progresses in early diagnosis and therapeutic strategies, prognosis for patients with advanced PCa remains poor. Noteworthily, a unique feature of healthy prostate is its highest level of zinc content among all soft tissues in the human body, which dramatically decreases during prostate tumorigenesis. To date, several reviews have suggested antitumor activities of zinc and its potential as a therapeutic strategy of PCa. However, an overview about the role of zinc and its signaling in PCa is needed. Here, we review literature related to the content, biological function, compounds and clinical application of zinc in PCa. We first summarize zinc content in prostate tissue and sera of PCa patients with their clinical relevance. We then elaborate biological functions of zinc signaling in PCa on three main aspects, including cell proliferation, death and tumor metastasis. Finally, we discuss clinical applications of zinc-containing compounds and proteins involved in PCa signaling pathways. Based on currently available studies, we conclude that zinc plays a tumor suppressive role and can serve as a biomarker in PCa diagnosis and therapies.
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9.
Understanding the Mechanisms of Diet and Outcomes in Colon, Prostate, and Breast Cancer; Malignant Gliomas; and Cancer Patients on Immunotherapy.
Mann, S, Sidhu, M, Gowin, K
Nutrients. 2020;(8)
Abstract
Cancer patients often ask which foods would be best to consume to improve outcomes. This is a difficult question to answer as there are no case-controlled, prospective studies that control for confounding factors. Therefore, a literature review utilizing PubMed was conducted with the goal to find evidence-based support for certain diets in specific cancer patients-specifically, we reviewed data for colon cancer, prostate cancer, breast cancer, malignant gliomas, and cancer patients on immunotherapy. Improved outcomes in colon cancer and patients on immunotherapy were found with high-fiber diets. Improved outcomes in malignant gliomas were found with ketogenic diets. Improved outcomes in prostate cancer and breast cancer were found with plant-based diets. However, the data are not conclusive for breast cancer. Additionally, the increased intake of omega-3 fatty acids were also associated with better outcomes for prostate cancer. While current research, especially in humans, is minimal, the studies discussed in this review provide the groundwork for future research to further investigate the role of dietary intervention in improving cancer outcomes.
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10.
Metabolic Roles of Androgen Receptor and Tip60 in Androgen-Dependent Prostate Cancer.
Tan, KN, Avery, VM, Carrasco-Pozo, C
International journal of molecular sciences. 2020;(18)
Abstract
Androgen receptor (AR)-mediated signaling is essential for the growth and differentiation of the normal prostate and is the primary target for androgen deprivation therapy in prostate cancer. Tat interactive protein 60 kDa (Tip60) is a histone acetyltransferase that is critical for AR activation. It is well known that cancer cells rewire their metabolic pathways in order to sustain aberrant proliferation. Growing evidence demonstrates that the AR and Tip60 modulate key metabolic processes to promote the survival of prostate cancer cells, in addition to their classical roles. AR activation enhances glucose metabolism, including glycolysis, tricarboxylic acid cycle and oxidative phosphorylation, as well as lipid metabolism in prostate cancer. The AR also interacts with other metabolic regulators, including calcium/calmodulin-dependent kinase kinase 2 and mammalian target of rapamycin. Several studies have revealed the roles of Tip60 in determining cell fate indirectly by modulating metabolic regulators, such as c-Myc, hypoxia inducible factor 1α (HIF-1α) and p53 in various cancer types. Furthermore, Tip60 has been shown to regulate the activity of key enzymes in gluconeogenesis and glycolysis directly through acetylation. Overall, both the AR and Tip60 are master metabolic regulators that mediate cellular energy metabolism in prostate cancer, providing a framework for the development of novel therapeutic targets in androgen-dependent prostate cancer.