New Discoveries and Future Trend for Prostate Cancer Research and Treatment

A project collection of Cancers (ISSN 2072-6694). This project collection belongs to the section "Tumor Microenvironment".

Papers displayed on this page all arise from the same project. Editorial decisions were made independently of project staff and handled by the Editor-in-Chief or qualified Editorial Board members.

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Editor

Department of Pharmacology, Edward Via College of Osteopathic Medicine, University of Louisiana at Monroe, Monroe, LA 71203, USA
Interests: tumor biomarkers; investigational markers; prognosis; biochemical relapse; overall survival; clinical trials; advancement in biomarker discovery; bioinformatics and marker discovery; AI and biomarker discovery
Special Issues, Collections and Topics in MDPI journals

Project Overview

Dear Colleagues,

Globally, about 1,276,106 new cases of prostate cancer were recorded in 2018. In the United States, it is the most commonly diagnosed cancer in elderly men, with more than 191,930 cases that will be diagnosed and 33,330 estimated deaths in 2020. The development of castration-resistant PCa (CRPC) is a current major concern in PCa management, where most patients develop aggressive forms of tumors. The first option for treating CRPC patients is to use anti-androgen therapies such as Enzalutamide and Abiraterone. The development of aggressive and metastatic CRPC (mCRPC) suggests that there is an urgent need to promote studies that aim to understand the molecular mechanisms underlying these changes in tumor cells and their microenvironment and develop novel strategies for treating and improving the overall survival of prostate cancer patients.

In this Special Issue, we will cover the following research topics:

  1. the biological significance of key molecules that contribute to prostate cancer progression and metastasis and novel approaches to their molecular targeting;
  2. the role of the tumor microenvironment (tumor–stromal interaction) in promoting prostate cancer progression and recurrence;
  3. the discovery of novel and reliable prostate cancer biomarkers (diagnostic and prognostic);
  4. updates on therapeutic approaches, clinical trials, and FDA-approved drugs for the treatment of prostate cancer; and
  5. prostate cancer prevention and community awareness.

Prof. Dr. Zakaria Y. Abd Elmageed
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • prostate cancer
  • cancer stem cells
  • tumor microenvironment
  • biomarkers
  • therapeutic targets
  • drug resistance
  • cancer prevention

Published Papers (10 papers)

2023

Jump to: 2022, 2021

20 pages, 775 KiB  
Review
Insights into the Human Microbiome and Its Connections with Prostate Cancer
by Raluca Munteanu, Richard-Ionut Feder, Anca Onaciu, Vlad Cristian Munteanu, Cristina-Adela Iuga and Diana Gulei
Cancers 2023, 15(9), 2539; https://doi.org/10.3390/cancers15092539 - 28 Apr 2023
Cited by 2 | Viewed by 1714
Abstract
The human microbiome represents the diversity of microorganisms that live together at different organ sites, influencing various physiological processes and leading to pathological conditions, even carcinogenesis, in case of a chronic imbalance. Additionally, the link between organ-specific microbiota and cancer has attracted the [...] Read more.
The human microbiome represents the diversity of microorganisms that live together at different organ sites, influencing various physiological processes and leading to pathological conditions, even carcinogenesis, in case of a chronic imbalance. Additionally, the link between organ-specific microbiota and cancer has attracted the interest of numerous studies and projects. In this review article, we address the important aspects regarding the role of gut, prostate, urinary and reproductive system, skin, and oral cavity colonizing microorganisms in prostate cancer development. Various bacteria, fungi, virus species, and other relevant agents with major implications in cancer occurrence and progression are also described. Some of them are assessed based on their values of prognostic or diagnostic biomarkers, while others are presented for their anti-cancer properties. Full article
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19 pages, 4699 KiB  
Article
Combination Modality Using Quercetin to Enhance the Efficacy of Docetaxel in Prostate Cancer Cells
by Satish Sharma, Katherine Cwiklinski, Supriya D. Mahajan, Stanley A. Schwartz and Ravikumar Aalinkeel
Cancers 2023, 15(3), 902; https://doi.org/10.3390/cancers15030902 - 31 Jan 2023
Cited by 3 | Viewed by 1754
Abstract
The standard of care chemotherapy drug presently used to treat castration-resistant prostate cancer (CRPC), docetaxel (Doc), also develops chemoresistance, thereby reducing its clinical utility. Since resistance to chemotherapy drugs can be overcome by co-treatment with plant-based bio-active compounds we undertook the present study [...] Read more.
The standard of care chemotherapy drug presently used to treat castration-resistant prostate cancer (CRPC), docetaxel (Doc), also develops chemoresistance, thereby reducing its clinical utility. Since resistance to chemotherapy drugs can be overcome by co-treatment with plant-based bio-active compounds we undertook the present study to evaluate if quercetin (Que), a flavonoid present in plants such as onions, apples, olives, and grapes can enhance the efficacy of Doc. We studied the separate and combined effects of Que and Doc at different doses and different combination approaches in two different prostate cancer cell lines, DU-145 (moderately aggressive) and PC-3 (very aggressive), and assessed the effects of these combinations on viability, proliferation, and apoptosis. Monotherapy with these drugs showed dose-dependent cytotoxicity; however, only Doc monotherapy showed a statistically significant difference in IC50 levels (IC50 = 4.05 ± 0.52 nM for PC-3 and IC50 = 2.26 ± 0.22 nM for DU-145). In combination treatment, we used three different treatment approaches (TAP). The concentrations and range analyzed were chosen based on the approximate cytotoxicity of 30–50% when the drugs were used individually. Our observations indicate that the most beneficial effect of the Que and Doc combination was obtained with the TAP-2 approach, which is pre-treatment with all doses of Que for 24 h followed by low doses of Doc for another 24 h. Using this approach, we observed synergism at low concentrations of Doc (0.5 and 1.0 nM) and all concentrations of Que. An additive effect was observed at moderate and high concentrations of Doc (1.5, 2.0, and 2.5 nM) and all concentrations of Que in both cell lines. The TAP-2 strategy was also helpful in overcoming Doc resistance in resistant CaP cells. In summary, Que improved the therapeutic effect of Doc in CRPC, and it is proposed that this improvement is mediated through multiple mechanisms. This study provides a novel therapeutic modality for an effective combination using Doc and Que to enhance the efficacy of Doc in an innocuous manner for Doc resistance and CRPC treatment. Full article
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2022

Jump to: 2023, 2021

21 pages, 4537 KiB  
Review
Obesity-Related Cross-Talk between Prostate Cancer and Peripheral Fat: Potential Role of Exosomes
by Shangzhi Feng, Kecheng Lou, Cong Luo, Junrong Zou, Xiaofeng Zou and Guoxi Zhang
Cancers 2022, 14(20), 5077; https://doi.org/10.3390/cancers14205077 - 17 Oct 2022
Cited by 7 | Viewed by 1733
Abstract
The molecular mechanisms of obesity-induced cancer progression have been extensively explored because of the significant increase in obesity and obesity-related diseases worldwide. Studies have shown that obesity is associated with certain features of prostate cancer. In particular, bioactive factors released from periprostatic adipose [...] Read more.
The molecular mechanisms of obesity-induced cancer progression have been extensively explored because of the significant increase in obesity and obesity-related diseases worldwide. Studies have shown that obesity is associated with certain features of prostate cancer. In particular, bioactive factors released from periprostatic adipose tissues mediate the bidirectional communication between periprostatic adipose tissue and prostate cancer. Moreover, recent studies have shown that extracellular vesicles have a role in the relationship between tumor peripheral adipose tissue and cancer progression. Therefore, it is necessary to investigate the feedback mechanisms between prostate cancer and periglandular adipose and the role of exosomes as mediators of signal exchange to understand obesity as a risk factor for prostate cancer. This review summarizes the two-way communication between prostate cancer and periglandular adipose and discusses the potential role of exosomes as a cross-talk and the prospect of using adipose tissue as a means to obtain exosomes in vitro. Therefore, this review may provide new directions for the treatment of obesity to suppress prostate cancer. Full article
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25 pages, 2052 KiB  
Review
Prostate Cancer Tumor Stroma: Responsibility in Tumor Biology, Diagnosis and Treatment
by Luis O. González, Noemi Eiro, Maria Fraile, Nana Beridze, Andres R. Escaf, Safwan Escaf, Jesús M. Fernández-Gómez and Francisco J. Vizoso
Cancers 2022, 14(18), 4412; https://doi.org/10.3390/cancers14184412 - 11 Sep 2022
Cited by 4 | Viewed by 2065
Abstract
Prostate cancer (PCa) is a common cancer among males globally, and its occurrence is growing worldwide. Clinical decisions about the combination of therapies are becoming highly relevant. However, this is a heterogeneous disease, ranging widely in prognosis. Therefore, new approaches are needed based [...] Read more.
Prostate cancer (PCa) is a common cancer among males globally, and its occurrence is growing worldwide. Clinical decisions about the combination of therapies are becoming highly relevant. However, this is a heterogeneous disease, ranging widely in prognosis. Therefore, new approaches are needed based on tumor biology, from which further prognostic assessments can be established and complementary strategies can be identified. The knowledge of both the morphological structure and functional biology of the PCa stroma compartment can provide new diagnostic, prognostic or therapeutic possibilities. In the present review, we analyzed the aspects related to the tumor stromal component (both acellular and cellular) in PCa, their influence on tumor behavior and the therapeutic response and their consideration as a new therapeutic target. Full article
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17 pages, 339 KiB  
Review
Active Surveillance in Intermediate-Risk Prostate Cancer: A Review of the Current Data
by Leandro Blas, Masaki Shiota and Masatoshi Eto
Cancers 2022, 14(17), 4161; https://doi.org/10.3390/cancers14174161 - 27 Aug 2022
Cited by 2 | Viewed by 1950
Abstract
Active surveillance (AS) is a monitoring strategy to avoid or defer curative treatment, minimizing the side effects of radiotherapy and prostatectomy without compromising survival. AS in intermediate-risk prostate cancer (PC) has increasingly become used. There is heterogeneity in intermediate-risk PC patients. Some of [...] Read more.
Active surveillance (AS) is a monitoring strategy to avoid or defer curative treatment, minimizing the side effects of radiotherapy and prostatectomy without compromising survival. AS in intermediate-risk prostate cancer (PC) has increasingly become used. There is heterogeneity in intermediate-risk PC patients. Some of them have an aggressive clinical course and require active treatment, while others have indolent disease and may benefit from AS. However, intermediate-risk patients have an increased risk of metastasis, and the proper way to select the best candidates for AS is unknown. In addition, there are several differences between AS protocols in inclusion criteria, monitoring follow-up, and triggers for active treatment. A few large series and randomized trials are under investigation. Therefore, more research is needed to establish an optimal therapeutic strategy for patients with intermediate-risk disease. This study summarizes the current data on patients with intermediate-risk PC under AS, recent findings, and discusses future directions. Full article
11 pages, 2137 KiB  
Article
Two Decades of Active Surveillance for Prostate Cancer in a Single-Center Cohort: Favorable Outcomes after Transurethral Resection of the Prostate
by Sarah Hagmann, Venkat Ramakrishnan, Alexander Tamalunas, Marc Hofmann, Moritz Vandenhirtz, Silvan Vollmer, Jsmea Hug, Philipp Niggli, Antonio Nocito, Rahel A. Kubik-Huch, Kurt Lehmann and Lukas John Hefermehl
Cancers 2022, 14(2), 368; https://doi.org/10.3390/cancers14020368 - 12 Jan 2022
Cited by 8 | Viewed by 2120
Abstract
Objective: To report the outcomes of active surveillance (AS) for low-risk prostate cancer (PCa) in a single-center cohort. Patients and Methods: This is a prospective, single-center, observational study. The cohort included all patients who underwent AS for PCa between December 1999 and December [...] Read more.
Objective: To report the outcomes of active surveillance (AS) for low-risk prostate cancer (PCa) in a single-center cohort. Patients and Methods: This is a prospective, single-center, observational study. The cohort included all patients who underwent AS for PCa between December 1999 and December 2020 at our institution. Follow-up appointments (FU) ended in February 2021. Results: A total of 413 men were enrolled in the study, and 391 had at least one FU. Of those who followed up, 267 had PCa diagnosed by transrectal ultrasound (TRUS)-guided biopsy (T1c: 68.3%), while 124 were diagnosed after transurethral resection of the prostate (TURP) (T1a/b: 31.7%). Median FU was 46 months (IQR 25–90). Cancer specific survival was 99.7% and overall survival was 92.3%. Median reclassification time was 11.2 years. After 20 years, 25% of patients were reclassified within 4.58 years, 6.6% opted to switch to watchful waiting, 4.1% died, 17.4% were lost to FU, and 46.8% remained on AS. Those diagnosed by TRUS had a significantly higher reclassification rate than those diagnosed by TURP (p < 0.0001). Men diagnosed by targeted MRI/TRUS fusion biopsy tended to have a higher reclassification probability than those diagnosed by conventional template biopsies (p = 0.083). Conclusions: Our single-center cohort spanning over two decades revealed that AS remains a safe option for low-risk PCa even in the long term. Approximately half of AS enrollees will eventually require definitive treatment due to disease progression. Men with incidental prostate cancer were significantly less likely to have disease progression. Full article
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2021

Jump to: 2023, 2022

29 pages, 1453 KiB  
Review
Molecular Imaging in Primary Staging of Prostate Cancer Patients: Current Aspects and Future Trends
by Reyhaneh Manafi-Farid, Shaghayegh Ranjbar, Zahra Jamshidi Araghi, Julia Pilz, Gregor Schweighofer-Zwink, Christian Pirich and Mohsen Beheshti
Cancers 2021, 13(21), 5360; https://doi.org/10.3390/cancers13215360 - 26 Oct 2021
Cited by 13 | Viewed by 2906
Abstract
Accurate primary staging is the cornerstone in all malignancies. Different morphological imaging modalities are employed in the evaluation of prostate cancer (PCa). Regardless of all developments in imaging, invasive histopathologic evaluation is still the standard method for the detection and staging of the [...] Read more.
Accurate primary staging is the cornerstone in all malignancies. Different morphological imaging modalities are employed in the evaluation of prostate cancer (PCa). Regardless of all developments in imaging, invasive histopathologic evaluation is still the standard method for the detection and staging of the primary PCa. Magnetic resonance imaging (MRI) and computed tomography (CT) play crucial roles; however, functional imaging provides additional valuable information, and it is gaining ever-growing acceptance in the management of PCa. Targeted imaging with different radiotracers has remarkably evolved in the past two decades. [111In]In-capromab pendetide scintigraphy was a new approach in the management of PCa. Afterwards, positron emission tomography (PET) tracers such as [11C/18F]choline and [11C]acetate were developed. Nevertheless, none found a role in the primary staging. By introduction of the highly sensitive small molecule prostate-specific membrane antigen (PSMA) PET/CT, as well as recent developments in MRI and hybrid PET/MRI systems, non-invasive staging of PCa is being contemplated. Several studies investigated the role of these sophisticated modalities in the primary staging of PCa, showing promising results. Here, we recapitulate the role of targeted functional imaging. We briefly mention the most popular radiotracers, their diagnostic accuracy in the primary staging of PCa, and impact on patient management. Full article
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19 pages, 1739 KiB  
Article
Small Extracellular Vesicle-Derived microRNAs Stratify Prostate Cancer Patients According to Gleason Score, Race and Associate with Survival of African American and Caucasian Men
by Hamdy E. A. Ali, Mohamed S. A. Gaballah, Rofaida Gaballa, Shahenda Mahgoub, Zeinab A. Hassan, Eman A. Toraih, Bettina F. Drake and Zakaria Y. Abd Elmageed
Cancers 2021, 13(20), 5236; https://doi.org/10.3390/cancers13205236 - 19 Oct 2021
Cited by 7 | Viewed by 1873
Abstract
The utility of small extracellular vesicles (sEVs)-derived microRNAs (miRs) to segregate prostate cancer (PCa) patients according to tumor aggressiveness and ancestral background has not been fully investigated. Thus, we aimed to determine the diagnostic and prognostic utility of sEV-associated miRs in identifying aggressive [...] Read more.
The utility of small extracellular vesicles (sEVs)-derived microRNAs (miRs) to segregate prostate cancer (PCa) patients according to tumor aggressiveness and ancestral background has not been fully investigated. Thus, we aimed to determine the diagnostic and prognostic utility of sEV-associated miRs in identifying aggressive PCa in African American (AA) and Caucasian (CA) men. Using a training cohort, miR profiling was performed on sEVs isolated from plasma of PCa patients. Top-ranked sEV-associated miRs were then validated in 150 plasma samples (75 AA and 75 CA) collected from two independent cohorts; NIH (n = 90) and Washington University (n = 60) cohorts. Receiver operating characteristic (ROC) curve, Kaplan–Meier and Cox proportional hazards regression were used to assess these miRs as clinical biomarkers. Among nine top-ranked sEV-associated miRs, miR-6068 and miR-1915-3p were enriched in sEVs collected from PCa patients compared to healthy volunteers. Moreover, miR-6716-5p and miR-3692-3p segregated AA from CA men and low from high Gleason score (GS), respectively. Upregulation of sEV-associated miR-1915-3p, miR-3692-3p and miR-5001-5p was associated with improved survival time, and only miR-1915-3p was associated with longer recurrence-free survival (RFS) as an independent prognostic marker. Taken together, we identified novel sEV-associated miRs that can differentiate PCa patients from normal, AA from CA and high from low GS and predicts RFS. Full article
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24 pages, 10830 KiB  
Article
Genetic Suppressor Element 1 (GSE1) Promotes the Oncogenic and Recurrent Phenotypes of Castration-Resistant Prostate Cancer by Targeting Tumor-Associated Calcium Signal Transducer 2 (TACSTD2)
by Oluwaseun Adebayo Bamodu, Yuan-Hung Wang, Chen-Hsun Ho, Su-Wei Hu, Chia-Da Lin, Kai-Yi Tzou, Wen-Ling Wu, Kuan-Chou Chen and Chia-Chang Wu
Cancers 2021, 13(16), 3959; https://doi.org/10.3390/cancers13163959 - 05 Aug 2021
Cited by 7 | Viewed by 2496
Abstract
Background: prostate cancer (PCa) is a principal cause of cancer-related morbidity and mortality. Castration resistance and metastasis are clinical challenges and continue to impede therapeutic success, despite diagnostic and therapeutic advances. There are reports of the oncogenic activity of genetic suppressor element (GSE)1 [...] Read more.
Background: prostate cancer (PCa) is a principal cause of cancer-related morbidity and mortality. Castration resistance and metastasis are clinical challenges and continue to impede therapeutic success, despite diagnostic and therapeutic advances. There are reports of the oncogenic activity of genetic suppressor element (GSE)1 in breast and gastric cancers; however, its role in therapy resistance, metastasis, and susceptibility to disease recurrence in PCa patients remains unclear. Objective: this study investigated the role of aberrantly expressed GSE1 in the metastasis, therapy resistance, relapse, and poor prognosis of advanced PCa. Methods: we used a large cohort of multi-omics data and in vitro, ex vivo, and in vivo assays to investigate the potential effect of altered GSE1 expression on advanced/castration-resistant PCa (CRPC) treatment responses, disease progression, and prognosis. Results: using a multi-cohort approach, we showed that GSE1 is upregulated in PCa, while tumor-associated calcium signal transducer 2 (TACSTD2) is downregulated. Moreover, the direct, but inverse, correlation interaction between GSE1 and TACSTD2 drives metastatic disease, castration resistance, and disease progression and modulates the clinical and immune statuses of patients with PCa. Patients with GSE1highTACSTD2low expression are more prone to recurrence and disease-specific death than their GSE1lowTACSTD2high counterparts. Interestingly, we found that the GSE1–TACSTD2 expression profile is associated with the therapy responses and clinical outcomes in patients with PCa, especially those with metastatic/recurrent disease. Furthermore, we demonstrate that the shRNA-mediated targeting of GSE1 (shGSE1) significantly inhibits cell proliferation and attenuates cell migration and tumorsphere formation in metastatic PC3 and DU145 cell lines, with an associated suppression of VIM, SNAI2, and BCL2 and the concomitant upregulation of TACSTD2 and BAX. Moreover, shGSE1 enhances sensitivity to the antiandrogens abiraterone and enzalutamide in vitro and in vivo. Conclusion: these data provide preclinical evidence of the oncogenic role of dysregulated GSE1–TACSTD2 signaling and show that the molecular or pharmacological targeting of GSE1 is a workable therapeutic strategy for inhibiting androgen-driven oncogenic signals, re-sensitizing CRPC to treatment, and repressing the metastatic/recurrent phenotypes of patients with PCa. Full article
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18 pages, 785 KiB  
Review
The Influence of Anti-Diabetic Drugs on Prostate Cancer
by Miłosz Knura, Wojciech Garczorz, Adam Borek, Franciszek Drzymała, Krystian Rachwał, Kurian George and Tomasz Francuz
Cancers 2021, 13(8), 1827; https://doi.org/10.3390/cancers13081827 - 12 Apr 2021
Cited by 12 | Viewed by 4336
Abstract
The incidences of prostate cancer (PC) and diabetes are increasing, with a sustained trend. The occurrence of PC and type 2 diabetes mellitus (T2DM) is growing with aging. The correlation between PC occurrence and diabetes is noteworthy, as T2DM is correlated with a [...] Read more.
The incidences of prostate cancer (PC) and diabetes are increasing, with a sustained trend. The occurrence of PC and type 2 diabetes mellitus (T2DM) is growing with aging. The correlation between PC occurrence and diabetes is noteworthy, as T2DM is correlated with a reduced risk of incidence of prostate cancer. Despite this reduction, diabetes mellitus increases the mortality in many cancer types, including prostate cancer. The treatment of T2DM is based on lifestyle changes and pharmacological management. Current available drugs, except insulin, are aimed at increasing insulin secretion (sulfonylureas, incretin drugs), improving insulin sensitivity (biguanides, thiazolidinediones), or increasing urinary glucose excretion (gliflozin). Comorbidities should be taken into consideration during the treatment of T2DM. This review describes currently known information about the mechanism and impact of commonly used antidiabetic drugs on the incidence and progression of PC. Outcomes of pre-clinical studies are briefly presented and their correlations with available clinical trials have also been observed. Available reports and meta-analyses demonstrate that most anti-diabetic drugs do not increase the risk during the treatment of patients with PC. However, some reports show a potential advantage of treatment of T2DM with specific drugs. Based on clinical reports, use of metformin should be considered as a therapeutic option. Moreover, anticancer properties of metformin were augmented while combined with GLP-1 analogs. Full article
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