Prostate Cancer: Genetics, Epigenetics and the Need for Immunological Biomarkers

Rafikova, Guzel; Gilyazova, I. R.; Enikeeva, Kadriia; Pavlov, V. N.; Kzhyshkowska, Julia

doi:10.20944/preprints202306.1223.v1

Cited by 4 publications

(1 citation statement)

References 24 publications

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“…Prostate cancer ranks as the second most common male cancer globally (Zhu et al, 2023), with 1,414,259 new cases of prostate cancer (PC) worldwide and 3,75,304 deaths from this type of cancer in 2020 according to the Global Cancer Observatory (Bergengren et al, 2023;Rafikova et al, 2023). Unfortunately, prostate cancer stands as one of the leading causes of cancer-related mortality in men (Rebello et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Mechanism of baicalein in treatment of castration-resistant prostate cancer based on network pharmacology and cell experiments

Dou,

Cui,

Zhou

et al. 2024

Front. Pharmacol.

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ObjectiveBaicalein, one of the most abundant flavonoids found in Chinese herb Scutellaria baicalensis Georgi, exhibits pharmacological activities against various cancers. However, the precise pharmacological mechanism of baicalein in treating castration-resistant prostate cancer (CRPC) remains elusive. This study aimed to elucidate the potential mechanism of baicalein against CRPC through a combination of network pharmacology and experimental approaches, thereby providing new avenues for research in CRPC treatment.MethodsThe pharmacological and molecular properties of baicalein were obtained using the TCMSP database. Baicalein-related targets were collected from multiple sources including SwissTargetPrediction, PharmMapper and CTD. Targets related to CRPC were acquired from DisGeNET, GeneCards, and CTD. The protein-protein interaction (PPI) was analyzed using STRING 11.5, and Cytoscape 3.7.2 software was utilized to explore the core targets of baicalein on CRPC. GO and KEGG pathway enrichment analysis were performed using DAVID database. Cell experiments were carried out to confirm the validity of the targets.ResultsA total of 131 potential targets of baicalein for the treatment of CRPC were obtained. Among them, TP53, AKT1, ALB, CASP3, and HSP90AA1, etc., were recognized as core targets by Cytoscape 3.7.2. GO function enrichment analysis yielded 926 entries, including 703 biological process (BP) terms, 84 cellular component (CC) terms and 139 molecular function (MF) terms. The KEGG pathway enrichment analysis unveiled 159 signaling pathways, mainly involved in Pathways in cancer, prostate cancer, AGE-RAGE signaling pathway in diabetic complications, TP53 signaling pathway, and PI3K-Akt signaling pathway, etc. Cell experiments confirmed that baicalein may inhibit the proliferation of CRPC cells and induce cell cycle arrest in the G1 phase. This effect could be associated with the TP53/CDK2/cyclin E1 pathway. In addition, the results of CETSA suggest that baicalein may directly bind to TP53.ConclusionBased on network pharmacology analysis and cell experiments, we have predicted and validated the potential targets and related pathways of baicalein for CRPC treatment. This comprehensive approach provides a scientific basis for elucidating the molecular mechanism underlying the action of baicalein in CRPC treatment. Furthermore, these findings offer valuable insights and serve as a reference for the research and development of novel anti-CRPC drugs.

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Section: Introductionmentioning

confidence: 99%

Mechanism of baicalein in treatment of castration-resistant prostate cancer based on network pharmacology and cell experiments

Dou,

Cui,

Zhou

et al. 2024

Front. Pharmacol.

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Prognostic Value of PlGF Upregulation in Prostate Cancer

Scimeca,

Giacobbi,

Servadei

et al. 2024

Biomedicines

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Background: Prostate cancer (PCa) is the second most commonly diagnosed cancer in men worldwide, with metastasis, particularly to bone, being the primary cause of mortality. Currently, prognostic markers like PSA levels and Gleason classification are limited in predicting metastasis, emphasizing the need for novel clinical biomarkers. New molecules predicting tumor progression have been identified over time. Some, such as the immune checkpoint inhibitors (ICIs) PD-1/PD-L1, have become valid markers as theranostic tools essential for prognosis and drug target therapy. However, despite the success of ICIs as an anti-cancer therapy for solid tumors, their efficacy in treating bone metastases has mainly proven ineffective, suggesting intrinsic resistance to this therapy in the bone microenvironment. This study explores the potential of immunological intratumoral biomarkers, focusing on placental growth factor (PlGF), Vascular Endothelial Growth Factor Receptor 1 (VEGFR1), and Programmed Cell Death Protein 1 (PD-1), in predicting bone metastasis formation. Methods: we analyzed PCa samples from patients with and without metastasis by immunohistochemical analysis. Results: Results revealed that PlGF expression is significantly higher in primary tumors of patients that developed metastasis within five years from the histological diagnosis. Additionally, PlGF expression correlates with increased VEGFR1 and PD-1 levels, as well as the presence of intratumoral M2 macrophages. Conclusions: These findings suggest that PlGF contributes to an immunosuppressive environment, thus favoring tumor progression and metastatic process. Results here highlight the potential of integrating these molecular markers with existing prognostic tools to enhance the accuracy of metastasis prediction in PCa. By identifying patients at risk for metastasis, clinicians can tailor treatment strategies more effectively, potentially improving survival outcomes and quality of life. This study underscores the importance of further research into the role of intratumoral biomarkers in PCa management.

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The Role of Curcumin in Cancer: A Focus on the PI3K/Akt Pathway

Zoi,

Kyritsis,

Galani

et al. 2024

Cancers

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Cancer is a life-threatening disease and one of the leading causes of death worldwide. Despite significant advancements in therapeutic options, most available anti-cancer agents have limited efficacy. In this context, natural compounds with diverse chemical structures have been investigated for their multimodal anti-cancer properties. Curcumin is a polyphenol isolated from the rhizomes of Curcuma longa and has been widely studied for its anti-inflammatory, anti-oxidant, and anti-cancer effects. Curcumin acts on the regulation of different aspects of cancer development, including initiation, metastasis, angiogenesis, and progression. The phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) pathway is a key target in cancer therapy, since it is implicated in initiation, proliferation, and cancer cell survival. Curcumin has been found to inhibit the PI3K/Akt pathway in tumor cells, primarily via the regulation of different key mediators, including growth factors, protein kinases, and cytokines. This review presents the therapeutic potential of curcumin in different malignancies, such as glioblastoma, prostate and breast cancer, and head and neck cancers, through the targeting of the PI3K/Akt signaling pathway.

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Prostate Cancer: Genetics, Epigenetics and the Need for Immunological Biomarkers

Cited by 4 publications

References 24 publications

Mechanism of baicalein in treatment of castration-resistant prostate cancer based on network pharmacology and cell experiments

Mechanism of baicalein in treatment of castration-resistant prostate cancer based on network pharmacology and cell experiments

Prognostic Value of PlGF Upregulation in Prostate Cancer

The Role of Curcumin in Cancer: A Focus on the PI3K/Akt Pathway

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