Metastatic Prostate Cancer: Interaction with Tumors and Their Microenvironments

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

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 10299

Special Issue Editor


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Guest Editor
Department of Urology, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan
Interests: prostate cancer; castration-resistant; therapy

Special Issue Information

Dear Colleagues,

For the sake of the advancement of our understanding of genetic abnormalities and mechanisms of prostate cancer progression, the clinical approach to metastatic advanced prostate cancer has dramatically changed in the last several years. However, the prognosis of metastatic prostate cancer is still not acceptable, and we should continue our efforts to understand the mechanisms of metastasis and progression of prostate cancer. Only a basic understanding can improve the prognosis of patients with metastatic prostate cancer, and we believe that in the future, we will be able to overcome this difficult disease.

The aim of this Special Issue is to focus on our understanding of prostate cancer metastasis, especially focusing on interactions with cancer cells and microenvironments, and we hope that this issue will be a guidepost to elucidate the mechanism of prostate cancer metastasis and progression.

In this Special Issue, original research articles and reviews are welcome.  Research areas may include the following:

  • Basic and clinical research of prostate cancer progression and metastasis is welcome. Articles with regard to interaction with cancer cells and tumor microenvironments are especially requested;
  • Review articles with regard to immunology or gut microbiota related to prostate cancer metastasis/progression are also welcome.

We look forward to receiving your contributions.

Dr. Takahiro Inoue
Guest Editor

Manuscript Submission Information

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Keywords

  • prostate cancer
  • metastasis
  • tumor microenvironment
  • castration resistance

Published Papers (4 papers)

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Review

21 pages, 1877 KiB  
Review
Dissecting Microbiome-Derived SCFAs in Prostate Cancer: Analyzing Gut Microbiota, Racial Disparities, and Epigenetic Mechanisms
by Thabiso Victor Miya, Rahaba Marima, Botle Precious Damane, Elisa Marie Ledet and Zodwa Dlamini
Cancers 2023, 15(16), 4086; https://doi.org/10.3390/cancers15164086 - 14 Aug 2023
Cited by 2 | Viewed by 1801
Abstract
Prostate cancer (PCa) continues to be the most diagnosed cancer and the second primary cause of fatalities in men globally. There is an abundance of scientific evidence suggesting that the human microbiome, together with its metabolites, plays a crucial role in carcinogenesis and [...] Read more.
Prostate cancer (PCa) continues to be the most diagnosed cancer and the second primary cause of fatalities in men globally. There is an abundance of scientific evidence suggesting that the human microbiome, together with its metabolites, plays a crucial role in carcinogenesis and has a significant impact on the efficacy of anticancer interventions in solid and hematological cancers. These anticancer interventions include chemotherapy, immune checkpoint inhibitors, and targeted therapies. Furthermore, the microbiome can influence systemic and local immune responses using numerous metabolites such as short-chain fatty acids (SCFAs). Despite the lack of scientific data in terms of the role of SCFAs in PCa pathogenesis, recent studies show that SCFAs have a profound impact on PCa progression. Several studies have reported racial/ethnic disparities in terms of bacterial content in the gut microbiome and SCFA composition. These studies explored microbiome and SCFA racial/ethnic disparities in cancers such as colorectal, colon, cervical, breast, and endometrial cancer. Notably, there are currently no published studies exploring microbiome/SCFA composition racial disparities and their role in PCa carcinogenesis. This review discusses the potential role of the microbiome in PCa development and progression. The involvement of microbiome-derived SCFAs in facilitating PCa carcinogenesis and their effect on PCa therapeutic response, particularly immunotherapy, are discussed. Racial/ethnic differences in microbiome composition and SCFA content in various cancers are also discussed. Lastly, the effects of SCFAs on PCa progression via epigenetic modifications is also discussed. Full article
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13 pages, 584 KiB  
Review
Roles of the PARP Inhibitor in BRCA1 and BRCA2 Pathogenic Mutated Metastatic Prostate Cancer: Direct Functions and Modification of the Tumor Microenvironment
by Takahiro Inoue, Sho Sekito, Takumi Kageyama, Yusuke Sugino and Takeshi Sasaki
Cancers 2023, 15(9), 2662; https://doi.org/10.3390/cancers15092662 - 08 May 2023
Cited by 2 | Viewed by 2308
Abstract
Cancer cells frequently exhibit defects in DNA damage repair (DDR), leading to genomic instability. Mutations in DDR genes or epigenetic alterations leading to the downregulation of DDR genes can result in increased dependency on other DDR pathways. Therefore, DDR pathways could be a [...] Read more.
Cancer cells frequently exhibit defects in DNA damage repair (DDR), leading to genomic instability. Mutations in DDR genes or epigenetic alterations leading to the downregulation of DDR genes can result in increased dependency on other DDR pathways. Therefore, DDR pathways could be a treatment target for various cancers. In fact, polyadenosine diphosphatase ribose polymerase (PARP) inhibitors, such as olaparib (Lynparza®), have shown remarkable therapeutic efficacy against BRCA1/2-mutant cancers through synthetic lethality. Recent genomic analytical advancements have revealed that BRCA1/BRCA2 pathogenic variants are the most frequent mutations among DDR genes in prostate cancer. Currently, the PROfound randomized controlled trial is investigating the efficacy of a PARP inhibitor, olaparib (Lynparza®), in patients with metastatic castration-resistant prostate cancer (mCRPC). The efficacy of the drug is promising, especially in patients with BRCA1/BRCA2 pathogenic variants, even if they are in the advanced stage of the disease. However, olaparib (Lynparza®) is not effective in all BRCA1/2 mutant prostate cancer patients and inactivation of DDR genes elicits genomic instability, leading to alterations in multiple genes, which eventually leads to drug resistance. In this review, we summarize PARP inhibitors’ basic and clinical mechanisms of action against prostate cancer cells and discuss their effects on the tumor microenvironment. Full article
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16 pages, 2490 KiB  
Review
Epigenetic Modifications in Prostate Cancer Metastasis and Microenvironment
by Shouyi Zhang, Tao Shen and Yu Zeng
Cancers 2023, 15(8), 2243; https://doi.org/10.3390/cancers15082243 - 11 Apr 2023
Cited by 5 | Viewed by 1777
Abstract
The gradual evolution of prostate tissue from benign tumor to malignant lesion or distant metastasis is driven by intracellular epigenetic changes and the tumor microenvironment remodeling. With the continuous study of epigenetic modifications, these tumor-driving forces are being discovered and are providing new [...] Read more.
The gradual evolution of prostate tissue from benign tumor to malignant lesion or distant metastasis is driven by intracellular epigenetic changes and the tumor microenvironment remodeling. With the continuous study of epigenetic modifications, these tumor-driving forces are being discovered and are providing new treatments for cancer. Here we introduce the classification of epigenetic modification and highlight the role of epigenetic modification in tumor remodeling and communication of the tumor microenvironment. Full article
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14 pages, 1198 KiB  
Review
The Gut-Prostate Axis: A New Perspective of Prostate Cancer Biology through the Gut Microbiome
by Kazutoshi Fujita, Makoto Matsushita, Marco A. De Velasco, Koji Hatano, Takafumi Minami, Norio Nonomura and Hirotsugu Uemura
Cancers 2023, 15(5), 1375; https://doi.org/10.3390/cancers15051375 - 21 Feb 2023
Cited by 8 | Viewed by 3747
Abstract
Obesity and a high-fat diet are risk factors associated with prostate cancer, and lifestyle, especially diet, impacts the gut microbiome. The gut microbiome plays important roles in the development of several diseases, such as Alzheimer’s disease, rheumatoid arthritis, and colon cancer. The analysis [...] Read more.
Obesity and a high-fat diet are risk factors associated with prostate cancer, and lifestyle, especially diet, impacts the gut microbiome. The gut microbiome plays important roles in the development of several diseases, such as Alzheimer’s disease, rheumatoid arthritis, and colon cancer. The analysis of feces from patients with prostate cancer by 16S rRNA sequencing has uncovered various associations between altered gut microbiomes and prostate cancer. Gut dysbiosis caused by the leakage of gut bacterial metabolites, such as short-chain fatty acids and lipopolysaccharide results in prostate cancer growth. Gut microbiota also play a role in the metabolism of androgen which could affect castration-resistant prostate cancer. Moreover, men with high-risk prostate cancer share a specific gut microbiome and treatments such as androgen-deprivation therapy alter the gut microbiome in a manner that favors prostate cancer growth. Thus, implementing interventions aiming to modify lifestyle or altering the gut microbiome with prebiotics or probiotics may curtail the development of prostate cancer. From this perspective, the “Gut–Prostate Axis” plays a fundamental bidirectional role in prostate cancer biology and should be considered when screening and treating prostate cancer patients. Full article
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