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Cancers
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Novel Drugs for Prostate Cancer
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Novel Drugs for Prostate Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Drug Development".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 8429

Special Issue Editor

Dr. Marco A. De Velasco

E-Mail Website
Guest Editor
Department of Genome Biology, Kindai University Faculty of Medicine, Osaka 589-8511, Japan
Interests: prostate cancer; immunotherapy; molecular targeted therapy; preclinical models; carcinogenesis

Special Issue Information

Dear Colleagues,

Prostate cancer is a slow growing malignancy that generally manifests in older men. Early-stage organ confined disease is readily treatable with surgery and radiation therapy; however, patients with locally advanced or metastatic cancers requires lifelong androgen deprivation therapy (ADT). Unfortunately, most patients develop resistance to ADT and eventually succumb to castration-resistant prostate cancer (CRPC). Efforts have been made to increase therapeutic options for men suffering with advanced prostate cancer. The efforts have paid off and as a result the therapeutic landscape for advanced prostate cancer now includes a broader range of treatment options that incorporates androgen receptor targeting agents (ARTAs, such as enzalutamide, abiraterone acetate, and darolutamide), cytotoxic chemotherapy (docetaxel and cabazitaxel), radioactive isotope (radium-233), poly-ADP-ribose polymerase inhibitors (PARPi, olaparib and rucaparib) and immunotherapy (sipuleucel-t). While these treatments improve outcomes, most patients will eventually relapse, and many others still fail to reap the benefits of the new treatment options. Hence, there is still an unmet need to develop novel treatment strategies.

Recent discoveries in molecular profiling of prostate cancers have uncovered potentially druggable targets. In addition, immunotherapy using immune checkpoint inhibitors has failed to improve outcomes of most men suffering with prostate cancer, however, some patients with immunologically active tumors do seem to respond to this form of therapy. Recent evidence suggests that reprograming the tumor microenvironment with pharmacological agents may invigorate antitumor responses. Thus, the outlook for developing novel therapeutic options for prostate cancer is promising.

This Special Issue will focus on novel therapeutic strategies being developed to manage advanced prostate cancer.  Submissions regarding preclinical and clinical research of novel compounds are welcome, as well as reviews and pilot studies focusing on new applications of existing drugs that could be utilized to improve current treatment options, molecular profiling for precision therapy and evaluating treatment responses, and reprograming the tumor microenvironment to bolster immunotherapy.

Dr. Marco A. De Velasco
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 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. 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
  • Castration-resistant prostate cancer
  • CRPC
  • Combination therapy
  • Immunotherapy
  • Androgen receptor
  • Molecular targeted therapy
  • Molecular profiling
  • Tumor microenvironment

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Published Papers (2 papers)

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Research

19 pages, 3798 KiB  
Article
An Aminosteroid Derivative Shows Higher In Vitro and In Vivo Potencies than Gold Standard Drugs in Androgen-Dependent Prostate Cancer Models
by Donald Poirier, Jenny Roy, René Maltais, Cindy Weidmann and Étienne Audet-Walsh
Cancers 2023, 15(11), 3033; https://doi.org/10.3390/cancers15113033 - 2 Jun 2023
Viewed by 5207
Abstract
The aminosteroid derivative RM-581 blocks with high potency the growth of androgen-dependent (AR+) prostate cancer VCaP, 22Rv1, and LAPC-4 cells. Notably, RM-581 demonstrated superior antiproliferative activity in LAPC-4 cells compared to enzalutamide and abiraterone, two drugs that exhibited a synergistic effect [...] Read more.
The aminosteroid derivative RM-581 blocks with high potency the growth of androgen-dependent (AR+) prostate cancer VCaP, 22Rv1, and LAPC-4 cells. Notably, RM-581 demonstrated superior antiproliferative activity in LAPC-4 cells compared to enzalutamide and abiraterone, two drugs that exhibited a synergistic effect in combination with RM-581. These findings suggest that RM-581 may have an action that is not directly associated with the hormonal pathway of androgens. Furthermore, RM-581 completely blocks tumor growth in LAPC-4 xenografts when given orally at 3, 10, and 30 mg/kg in non-castrated (intact) nude mice. During this study, an accumulation of RM-581 was observed in tumors compared to plasma (3.3–10 folds). Additionally, the level of fatty acids (FA) increased in the tumors and livers of mice treated with RM-581 but not in plasma. The increase was greater in unsaturated FA (21–28%) than in saturated FA (7–11%). The most affected FA were saturated palmitic acid (+16%), monounsaturated oleic acid (+34%), and di-unsaturated linoleic acid (+56%), i.e., the 3 most abundant FA, with a total of 55% of the 56 FA measured. For cholesterol levels, there was no significant difference in the tumor, liver, or plasma of mice treated or not with RM-581. Another important result was the innocuity of RM-581 in mice during a 28-day xenograft experiment and a 7-week dose-escalation study, suggesting a favorable safety window for this new promising drug candidate when given orally. Full article
(This article belongs to the Special Issue Novel Drugs for Prostate Cancer)
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19 pages, 3161 KiB  
Article
α-Mangostin Promotes In Vitro and In Vivo Degradation of Androgen Receptor and AR-V7 Splice Variant in Prostate Cancer Cells
by Mirielle C. Nauman, Jong Hoon Won, Sakina M. Petiwala, Bhaskar Vemu, Hyun Lee, Maria Sverdlov and Jeremy J. Johnson
Cancers 2023, 15(7), 2118; https://doi.org/10.3390/cancers15072118 - 1 Apr 2023
Cited by 4 | Viewed by 2860
Abstract
A major limitation of current prostate cancer pharmacotherapy approaches is the inability of these compounds to target androgen receptor variants or mutants that develop during prostate cancer progression. The demand for novel therapeutics to prevent, slow, and treat prostate cancer is significant because [...] Read more.
A major limitation of current prostate cancer pharmacotherapy approaches is the inability of these compounds to target androgen receptor variants or mutants that develop during prostate cancer progression. The demand for novel therapeutics to prevent, slow, and treat prostate cancer is significant because FDA approved anti-androgens are associated with adverse events and can eventually drive drug-resistant prostate cancer. This study evaluated α-mangostin for its novel ability to degrade the androgen receptor and androgen receptor variants. α-Mangostin is one of more than 70 isoprenylated xanthones isolated from Garcinia mangostana that we have been evaluating for their anticancer potential. Prostate cancer cells treated with α-mangostin exhibited decreased levels of wild-type and mutated androgen receptors. Immunoblot, immunoprecipitation, and transfection experiments demonstrated that the androgen receptor was ubiquitinated and subsequently degraded via the proteasome, which we hypothesize occurs with the assistance of BiP, an ER chaperone protein that we have shown to associate with the androgen receptor. We also evaluated α-mangostin for its antitumor activity and promotion of androgen receptor degradation in vivo. In summary, our study demonstrates that androgen receptor degradation occurs through the novel activation of BiP and suggests a new therapeutic approach for prostate cancer. Full article
(This article belongs to the Special Issue Novel Drugs for Prostate Cancer)
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