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Biomedicines
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Advanced Research in Prostate Cancer
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Advanced Research in Prostate Cancer

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (28 February 2022) | Viewed by 19588

Special Issue Editor

Dr. Ruth Vinall

E-Mail Website
Guest Editor
Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, California Northstate University, Elk Grove, CA, USA
Interests: prostate cancer; bladder cancer; natural products research; biomarkers; targeted therapy; miRNA; mechanisms of chemoresistance
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Over the past few years, we have witnessed major advances in prostate cancer treatments. The trend, as for many cancer types, is moving toward the development and clinical usage of biomedicine-based approaches. For example, Sipuleucel-T, a prostate cancer vaccine which received FDA approval in 2010, is becoming more widely used in patients with metastatic disease. Pembrolizumab and Nivolumab, also immunotherapies, show much promise. Continued efforts in the area of natural products research indicate that natural bioactive products can help to reduce prostate cancer incidence and progression. Large-scale genomics projects have led to the ongoing development of several targeted therapies, and, importantly, the co-development of biomarkers will allow for the prediction and measurement of patient response. Lastly, implementation of innovative drug delivery technologies, for example, nanoparticles, is helping to improve drug response rates while minimizing off-target effects. This is an exciting time for prostate cancer research! This Special Edition of Biomedicines entitled ‘Advanced Research in Prostate Cancer’ will include reviews that describe major advances which have occurred in the treatment of prostate cancer over the past few years as well as original research articles that describe preclinical and/or translational studies which will support future advances.

On behalf of the Biomedicines journal, I invite you to submit a review article for this Special Edition. It would be an honor to work and co-publish with you. Articles should be focused on the development and usage, or potential usage, of biomedicines, including natural bioactive molecules, biologics, vaccines, and/or targeted therapies to treat prostate cancer. Articles which outline how genetic analyses can guide the development and use of these treatment options, or which describe innovative drug delivery strategies, are also welcomed.

Dr. Ruth Vinall
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. Biomedicines is an international peer-reviewed open access monthly 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 2600 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
  • immunotherapy
  • natural bioactive products
  • targeted therapies
  • vaccines
  • biologics

Related Special Issue

Published Papers (4 papers)

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Research

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19 pages, 3479 KiB  
Article
Validation of Cell-Free RNA and Circulating Tumor Cells for Molecular Marker Analysis in Metastatic Prostate Cancer
by Michael Ladurner, Manuel Wieser, Andrea Eigentler, Martin Seewald, Gabriele Dobler, Hannes Neuwirt, Mona Kafka, Isabel Heidegger, Wolfgang Horninger, Jasmin Bektic, Helmut Klocker, Peter Obrist and Iris E. Eder
Biomedicines 2021, 9(8), 1004; https://doi.org/10.3390/biomedicines9081004 - 12 Aug 2021
Cited by 5 | Viewed by 2881
Abstract
Since tissue material is often lacking in metastatic prostate cancer (mPCa), there is increasing interest in using liquid biopsies for treatment decision and monitoring therapy responses. The purpose of this study was to validate the usefulness of circulating tumor cells (CTCs) and plasma-derived [...] Read more.
Since tissue material is often lacking in metastatic prostate cancer (mPCa), there is increasing interest in using liquid biopsies for treatment decision and monitoring therapy responses. The purpose of this study was to validate the usefulness of circulating tumor cells (CTCs) and plasma-derived cell-free (cf) RNA as starting material for gene expression analysis through qPCR. CTCs were identified upon prostate-specific membrane antigen and/or cytokeratin positivity after enrichment with ScreenCell (Westford, Massachusetts, USA) filters or the microfluidic ParsortixTM (Guildford, Surrey, United Kingdom) system. Overall, 50% (28/56) of the patients had ≥5 CTCs/7.5 mL of blood. However, CTC count did not correlate with Gleason score, serum PSA, or gene expression. Notably, we observed high expression of CD45 in CTC samples after enrichment, which could be successfully eliminated through picking of single cells. Gene expression in picked CTCs was, however, rather low. In cfRNA from plasma, on the other hand, gene expression levels were higher compared to those found in CTCs. Moreover, we found that PSA was significantly increased in plasma-derived cfRNA of mPCa patients compared to healthy controls. High PSA expression was also associated with poor overall survival, indicating that using cfRNA from plasma could be used as a valuable tool for molecular expression analysis. Full article
(This article belongs to the Special Issue Advanced Research in Prostate Cancer)
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15 pages, 2506 KiB  
Article
Modulating the Heat Sensitivity of Prostate Cancer Cell Lines In Vitro: A New Impact for Focal Therapies
by Oliver Hahn, Franziska M. Heining, Jörn Janzen, Johanna C. R. Becker, Marina Bertlich, Paul Thelen, Josef J. Mansour, Stefan Duensing, Sascha Pahernik, Lutz Trojan and Ionel V. Popeneciu
Biomedicines 2020, 8(12), 585; https://doi.org/10.3390/biomedicines8120585 - 09 Dec 2020
Cited by 3 | Viewed by 2155
Abstract
Focal therapies such as high-intensity focused ultrasound (HiFU) are an emerging therapeutic option for prostate cancer (PCA). Thermal or mechanical effects mediate most therapies. Moreover, locally administered drugs such as bicalutamide or docetaxel are new focal therapeutic options. We assessed the impact of [...] Read more.
Focal therapies such as high-intensity focused ultrasound (HiFU) are an emerging therapeutic option for prostate cancer (PCA). Thermal or mechanical effects mediate most therapies. Moreover, locally administered drugs such as bicalutamide or docetaxel are new focal therapeutic options. We assessed the impact of such focal medical treatments on cell viability and heat sensitivity by pre-treating PCA cell lines and then gradually exposing them to heat. The individual heat response of the cell lines tested differed largely. Vertebral-Cancer of the Prostate (VCaP) cells showed an increase in metabolic activity at 40–50 °C. Androgen receptor (AR)-negative PC3 cells showed an increase at 51.3 °C and were overall more resistant to higher temperatures. Pre-treatment of VCaP cells with testosterone (VCaPrev) leads to a more PC3-like kinetic of the heat response. Pre-treatment with finasteride and bicalutamide did not cause changes in heat sensitivity in any cell line. Mitoxantrone treatment, however, shifted heat-induced proliferation loss to lower temperature in VCaP cells. Further analysis via RNAseq identified a possible correlation of heat resistance with H3K27me3-dependent gene regulation, which could be related to an increase in the histone methyltransferase EZH2 and a possible neuroendocrine differentiation. Pre-treatment with mitoxantrone might be a perspective for HiFU treatment. Further studies are needed to evaluate possible combinations with Hsp90 or EZH2 inhibitors. Full article
(This article belongs to the Special Issue Advanced Research in Prostate Cancer)
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16 pages, 1116 KiB  
Article
Genistein Combined Polysaccharide (GCP) Can Inhibit Intracrine Androgen Synthesis in Prostate Cancer Cells
by Neelu Batra, Anhao Sam, Tibebe Woldemariam, George Talbott, Ralph W. de Vere White, Paramita M. Ghosh, Nilesh W. Gaikwad, Simeon O. Kotchoni and Ruth L. Vinall
Biomedicines 2020, 8(8), 282; https://doi.org/10.3390/biomedicines8080282 - 11 Aug 2020
Cited by 7 | Viewed by 2874
Abstract
Our group and others have previously shown that genistein combined polysaccharide (GCP), an aglycone isoflavone-rich extract with high bioavailability and low toxicity, can inhibit prostate cancer (CaP) cell growth and survival as well as androgen receptor (AR) activity. We now elucidate the mechanism [...] Read more.
Our group and others have previously shown that genistein combined polysaccharide (GCP), an aglycone isoflavone-rich extract with high bioavailability and low toxicity, can inhibit prostate cancer (CaP) cell growth and survival as well as androgen receptor (AR) activity. We now elucidate the mechanism by which this may occur using LNCaP and PC-346C CaP cell lines; GCP can inhibit intracrine androgen synthesis in CaP cells. UPLC-MS/MS and qPCR analyses demonstrated that GCP can mediate a ~3-fold decrease in testosterone levels (p < 0.001) and cause decreased expression of intracrine androgen synthesis pathway enzymes (~2.5-fold decrease of 3βHSD (p < 0.001), 17βHSD (p < 0.001), CYP17A (p < 0.01), SRB1 (p < 0.0001), and StAR (p < 0.01)), respectively. Reverse-phase HPLC fractionation and bioassay identified three active GCP fractions. Subsequent NMR and LC-MS analysis of the fraction with the highest level of activity, fraction 40, identified genistein as the primary active component of GCP responsible for its anti-proliferative, pro-apoptotic, and anti-AR activity. GCP, fraction 40, and genistein all mediated at least a ~2-fold change in these biological activities relative to vehicle control (p < 0.001). Genistein caused similar decreases in the expression of 17βHSD and CYP17A (2.5-fold (p < 0.001) and 1.5-fold decrease (p < 0.01), respectively) compared to GCP, however it did not cause altered expression of the other intracrine androgen synthesis pathway enzymes; 3βHSD, SRB1, and StAR. Our combined data indicate that GCP and/or genistein may have clinical utility and that further pre-clinical studies are warranted. Full article
(This article belongs to the Special Issue Advanced Research in Prostate Cancer)
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Review

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19 pages, 2773 KiB  
Review
The Androgen Receptor in Prostate Cancer: Effect of Structure, Ligands and Spliced Variants on Therapy
by Elisabeth A. Messner, Thomas M. Steele, Maria Malvina Tsamouri, Nazila Hejazi, Allen C. Gao, Maria Mudryj and Paramita M. Ghosh
Biomedicines 2020, 8(10), 422; https://doi.org/10.3390/biomedicines8100422 - 15 Oct 2020
Cited by 42 | Viewed by 10751
Abstract
The androgen receptor (AR) plays a predominant role in prostate cancer (PCa) pathology. It consists of an N-terminal domain (NTD), a DNA-binding domain (DBD), a hinge region (HR), and a ligand-binding domain (LBD) that binds androgens, including testosterone (T) and dihydrotestosterone (DHT). Ligand [...] Read more.
The androgen receptor (AR) plays a predominant role in prostate cancer (PCa) pathology. It consists of an N-terminal domain (NTD), a DNA-binding domain (DBD), a hinge region (HR), and a ligand-binding domain (LBD) that binds androgens, including testosterone (T) and dihydrotestosterone (DHT). Ligand binding at the LBD promotes AR dimerization and translocation to the nucleus where the DBD binds target DNA. In PCa, AR signaling is perturbed by excessive androgen synthesis, AR amplification, mutation, or the formation of AR alternatively spliced variants (AR-V) that lack the LBD. Current therapies for advanced PCa include androgen synthesis inhibitors that suppress T and/or DHT synthesis, and AR inhibitors that prevent ligand binding at the LBD. However, AR mutations and AR-Vs render LBD-specific therapeutics ineffective. The DBD and NTD are novel targets for inhibition as both perform necessary roles in AR transcriptional activity and are less susceptible to AR alternative splicing compared to the LBD. DBD and NTD inhibition can potentially extend patient survival, improve quality of life, and overcome predominant mechanisms of resistance to current therapies. This review discusses various small molecule and other inhibitors developed against the DBD and NTD—and the current state of the available compounds in clinical development. Full article
(This article belongs to the Special Issue Advanced Research in Prostate Cancer)
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