Transcending frontiers in prostate cancer: the role of oncometabolites on epigenetic regulation, CSCs, and tumor microenvironment to identify new therapeutic strategies

doi:10.1186/s12964-023-01462-0

Review

. 2024 Jan 12;22(1):36.

doi: 10.1186/s12964-023-01462-0.

Transcending frontiers in prostate cancer: the role of oncometabolites on epigenetic regulation, CSCs, and tumor microenvironment to identify new therapeutic strategies

Giulia Ambrosini¹, Marco Cordani^{2

3}, Ali Zarrabi^{4

5}, Sergio Alcon-Rodriguez^{6

7

8}, Rosa M Sainz^{6

7

8}, Guillermo Velasco^{9

10}, Pedro Gonzalez-Menendez^{11

12

13}, Ilaria Dando¹⁴

Affiliations

¹ Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, 37134, Verona, Italy.
² Department of Biochemistry and Molecular Biology, Faculty of Biology, Complutense University, 28040, Madrid, Spain. mcordani@ucm.es.
³ Instituto de Investigaciones Sanitarias San Carlos (IdISSC), 28040, Madrid, Spain. mcordani@ucm.es.
⁴ Department of Biomedical Engineering, Faculty of Engineering & Natural Sciences, Istinye University, Istanbul, 34396, Turkey.
⁵ Department of Research Analytics, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, 600 077, India.
⁶ Departamento de Morfología y Biología Celular, School of Medicine, Julián Claveria 6, 33006, Oviedo, Spain.
⁷ Instituto Universitario de Oncología del Principado de Asturias (IUOPA), University of Oviedo, 33006, Oviedo, Spain.
⁸ Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias (HUCA), 33011, Oviedo, Spain.
⁹ Department of Biochemistry and Molecular Biology, Faculty of Biology, Complutense University, 28040, Madrid, Spain.
¹⁰ Instituto de Investigaciones Sanitarias San Carlos (IdISSC), 28040, Madrid, Spain.
¹¹ Departamento de Morfología y Biología Celular, School of Medicine, Julián Claveria 6, 33006, Oviedo, Spain. gonzalezmpedro@uniovi.es.
¹² Instituto Universitario de Oncología del Principado de Asturias (IUOPA), University of Oviedo, 33006, Oviedo, Spain. gonzalezmpedro@uniovi.es.
¹³ Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias (HUCA), 33011, Oviedo, Spain. gonzalezmpedro@uniovi.es.
¹⁴ Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, 37134, Verona, Italy. ilaria.dando@univr.it.

PMID: 38216942
PMCID: PMC10790277
DOI: 10.1186/s12964-023-01462-0

Review

Transcending frontiers in prostate cancer: the role of oncometabolites on epigenetic regulation, CSCs, and tumor microenvironment to identify new therapeutic strategies

Giulia Ambrosini et al. Cell Commun Signal. 2024.

. 2024 Jan 12;22(1):36.

doi: 10.1186/s12964-023-01462-0.

Authors

Affiliations

¹ Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, 37134, Verona, Italy.
² Department of Biochemistry and Molecular Biology, Faculty of Biology, Complutense University, 28040, Madrid, Spain. mcordani@ucm.es.
³ Instituto de Investigaciones Sanitarias San Carlos (IdISSC), 28040, Madrid, Spain. mcordani@ucm.es.
⁴ Department of Biomedical Engineering, Faculty of Engineering & Natural Sciences, Istinye University, Istanbul, 34396, Turkey.
⁵ Department of Research Analytics, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, 600 077, India.
⁶ Departamento de Morfología y Biología Celular, School of Medicine, Julián Claveria 6, 33006, Oviedo, Spain.
⁷ Instituto Universitario de Oncología del Principado de Asturias (IUOPA), University of Oviedo, 33006, Oviedo, Spain.
⁸ Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias (HUCA), 33011, Oviedo, Spain.
⁹ Department of Biochemistry and Molecular Biology, Faculty of Biology, Complutense University, 28040, Madrid, Spain.
¹⁰ Instituto de Investigaciones Sanitarias San Carlos (IdISSC), 28040, Madrid, Spain.
¹¹ Departamento de Morfología y Biología Celular, School of Medicine, Julián Claveria 6, 33006, Oviedo, Spain. gonzalezmpedro@uniovi.es.
¹² Instituto Universitario de Oncología del Principado de Asturias (IUOPA), University of Oviedo, 33006, Oviedo, Spain. gonzalezmpedro@uniovi.es.
¹³ Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Hospital Universitario Central de Asturias (HUCA), 33011, Oviedo, Spain. gonzalezmpedro@uniovi.es.
¹⁴ Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, 37134, Verona, Italy. ilaria.dando@univr.it.

PMID: 38216942
PMCID: PMC10790277
DOI: 10.1186/s12964-023-01462-0

Abstract

Prostate cancer, as one of the most prevalent malignancies in males, exhibits an approximate 5-year survival rate of 95% in advanced stages. A myriad of molecular events and mutations, including the accumulation of oncometabolites, underpin the genesis and progression of this cancer type. Despite growing research demonstrating the pivotal role of oncometabolites in supporting various cancers, including prostate cancer, the root causes of their accumulation, especially in the absence of enzymatic mutations, remain elusive. Consequently, identifying a tangible therapeutic target poses a formidable challenge. In this review, we aim to delve deeper into the implications of oncometabolite accumulation in prostate cancer. We center our focus on the consequential epigenetic alterations and impacts on cancer stem cells, with the ultimate goal of outlining novel therapeutic strategies.

Keywords: Cancer stem cells (CSCs); EMT; Epigenetic alterations; Metabolic Enzymes; Oncometabolites; Prostate cancer.

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Conflict of interest statement

The authors declare no competing interests.

Figures

**Fig. 1**
Scheme representing the role oncometabolites in prostate cancer with addition of other tissues, highlighting potential diagnostic tools

**Fig. 2**
Oncometabolites in the tumor microenvironment

See this image and copyright information in PMC

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References

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1. Sandhu S, Moore CM, Chiong E, Beltran H, Bristow RG, Williams SG. Prostate cancer. Lancet. 2021;398:1075–1090. doi: 10.1016/S0140-6736(21)00950-8. - DOI - PubMed
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1. Hakozaki Y, Yamada Y, Kawai T, Nakamura M, Takeshima Y, Iwaki T, et al. Time to castration resistance is a novel prognostic factor of cancer-specific survival in patients with nonmetastatic castration-resistant prostate cancer. Sci Rep. 2022;12:16202. doi: 10.1038/s41598-022-20319-z. - DOI - PMC - PubMed

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[1] Ittmann M. Anatomy and histology of the human and murine prostate. Cold Spring Harb Perspect Med. 2018;8:a030346. doi: 10.1101/cshperspect.a030346. - DOI - PMC - PubMed

[2] Ittmann M. Anatomy and histology of the human and murine prostate. Cold Spring Harb Perspect Med. 2018;8:a030346. doi: 10.1101/cshperspect.a030346. - DOI - PMC - PubMed

[3] Sandhu S, Moore CM, Chiong E, Beltran H, Bristow RG, Williams SG. Prostate cancer. Lancet. 2021;398:1075–1090. doi: 10.1016/S0140-6736(21)00950-8. - DOI - PubMed

[4] Sandhu S, Moore CM, Chiong E, Beltran H, Bristow RG, Williams SG. Prostate cancer. Lancet. 2021;398:1075–1090. doi: 10.1016/S0140-6736(21)00950-8. - DOI - PubMed

[5] Espiritu SMG, Liu LY, Rubanova Y, Bhandari V, Holgersen EM, Szyca LM, et al. The evolutionary landscape of localized prostate cancers drives clinical aggression. Cell. 2018;173:1003–1013.e15. doi: 10.1016/j.cell.2018.03.029. - DOI - PubMed

[6] Espiritu SMG, Liu LY, Rubanova Y, Bhandari V, Holgersen EM, Szyca LM, et al. The evolutionary landscape of localized prostate cancers drives clinical aggression. Cell. 2018;173:1003–1013.e15. doi: 10.1016/j.cell.2018.03.029. - DOI - PubMed

[7] Rawla P. Epidemiology of prostate cancer. World J Oncol. 2019;10:63–89. doi: 10.14740/wjon1191. - DOI - PMC - PubMed

[8] Rawla P. Epidemiology of prostate cancer. World J Oncol. 2019;10:63–89. doi: 10.14740/wjon1191. - DOI - PMC - PubMed

[9] Hakozaki Y, Yamada Y, Kawai T, Nakamura M, Takeshima Y, Iwaki T, et al. Time to castration resistance is a novel prognostic factor of cancer-specific survival in patients with nonmetastatic castration-resistant prostate cancer. Sci Rep. 2022;12:16202. doi: 10.1038/s41598-022-20319-z. - DOI - PMC - PubMed

[10] Hakozaki Y, Yamada Y, Kawai T, Nakamura M, Takeshima Y, Iwaki T, et al. Time to castration resistance is a novel prognostic factor of cancer-specific survival in patients with nonmetastatic castration-resistant prostate cancer. Sci Rep. 2022;12:16202. doi: 10.1038/s41598-022-20319-z. - DOI - PMC - PubMed

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Transcending frontiers in prostate cancer: the role of oncometabolites on epigenetic regulation, CSCs, and tumor microenvironment to identify new therapeutic strategies

Affiliations

Transcending frontiers in prostate cancer: the role of oncometabolites on epigenetic regulation, CSCs, and tumor microenvironment to identify new therapeutic strategies

Authors

Affiliations

Abstract

Conflict of interest statement

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