Investigating the Role of Mineralocorticoid Receptor Signaling in Cancer Biology in the Genomic Era

Konu, Özlen; Targen, Seniye

doi:10.5772/intechopen.87233

Cited by 3 publications

(3 citation statements)

References 91 publications

(96 reference statements)

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“…Further studies in this regard have debated this point based on concentration dependant effects of glucocorticoids which may vary across different types of cancer ranging from breast cancer to castration resistant prostate cancer [23][24][25][26][27][28]. The report by Nagata et al 2019 suggests an overall role of MR as Tumor-suppressors while also stating that this might change depending on the levels of MR expression on the cells of origin [29,30].…”

Section: Discussionmentioning

confidence: 99%

Steroid hormone receptor based gene delivery systems as potential oral cancer therapeutics

Bhattacharya,

Bharati,

Sakhare

et al. 2024

Biomed. Mater.

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Glucocorticoid and Mineralocorticoid receptors are principally ligand-dependent intracellular transcription factors that are known to influence the development and growth of many human cancers. Our study investigates the potential of these receptors to act as a target for oral cancer treatment since findings in this regard are sparse till date. Leveraging the aberrant behaviour of SHRs (Steroid Hormone Receptors) in cancer, we have targeted oral cancer cells in 2D-culture using liposomes containing both synthetic as well as crude, natural SHR ligands isolated from an aqueous Indian medicinal plant. Lipoplexes thus formulated demonstrated targeted transfectability as indicated by expression of GFP (Green Fluorescent Protein). Transfection of OSCC cells with exogenous, anticancer gene p53 lipoplexed with crude saponin-based liposome induced apoptosis of cancer cells via regulation of BAX and BCL2 protein levels at levels comparable with pre-established delivery systems based on synthetic SHR ligands. Our findings strongly indicate a possibility of developing plant saponin-based inexpensive delivery systems which would target cancer cells selectively with reduced risks of off target delivery and its side effects.

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Section: Discussionmentioning

confidence: 99%

Steroid hormone receptor based gene delivery systems as potential oral cancer therapeutics

Bhattacharya,

Bharati,

Sakhare

et al. 2024

Biomed. Mater.

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“…Consistent with this, and unlike prednisolone, AZD9567 had no effect on the serum sodium: potassium ratio. However, it should be noted that, in general, very few mineralocorticoid receptor transcriptomic published data exist, 14 and many genes are regulated by both glucocorticoid and mineralocorticoid receptors 15,16 . Indazole ethers are great tools to explore glucocorticoid receptor‐exclusive profiles, 17 but there are currently no equivalent tools for mineralocorticoid receptor‐exclusive profiles, and even aldosterone binds to the glucocorticoid receptor, albeit at a lower affinity than to the mineralocorticoid receptor 18 …”

Section: Discussionmentioning

confidence: 99%

AZD9567 versus prednisolone in patients with active rheumatoid arthritis: A phase IIa, randomized, double‐blind, efficacy, and safety study

van Laar,

Lei,

Safy‐Khan

et al. 2023

Clinical Translational Sci

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Oral corticosteroid use is limited by side effects, some caused by off‐target actions on the mineralocorticoid receptor that disrupt electrolyte balance. AZD9567 is a selective, nonsteroidal glucocorticoid receptor modulator. The efficacy, safety, and tolerability of AZD9567 and prednisolone were assessed in a phase IIa study. Anti‐inflammatory mechanism of action was also evaluated in vitro in monocytes from healthy donors. In this randomized, double‐blind, parallel‐group, multicenter study, patients with active rheumatoid arthritis were randomized 1:1 to AZD9567 40 mg or prednisolone 20 mg once daily orally for 14 days. The primary end point was change from baseline in DAS28‐CRP at day 15. Secondary end points included components of DAS28‐CRP, American College of Rheumatology (ACR) response criteria (ACR20, ACR50, and ACR70), and safety end points, including serum electrolytes. Overall, 21 patients were randomized to AZD9567 (n = 11) or prednisolone (n = 10), and all completed the study. As anticipated, AZD9567 had a similar efficacy profile to prednisolone, with no clinically meaningful (i.e., >1.0) difference in change from baseline to day 15 in DAS28‐CRP between AZD9567 and prednisolone (least‐squares mean difference: 0.47, 95% confidence interval: −0.49 to 1.43). Similar results were observed for the secondary efficacy end points. In vitro transcriptomic analysis showed that anti‐inflammatory responses were similar for AZD9567, prednisolone, and dexamethasone. Unlike prednisolone, AZD9567 had no effect on the serum sodium:potassium ratio. The safety profile was not different from that of prednisolone. Larger studies of longer duration are required to determine whether AZD9567 40 mg may in the future be an alternative to prednisolone in patients with inflammatory disease.

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“…The generalized tumor-suppressor role that has been attributed to MR based on findings from studies involving different cancer types is still under question and this requires a further in-depth understanding of the relationship between MR activity status in terms of its expression levels and patient survival in different cancers (Konu & Targen, 2019).…”

Section: Mr In Cancermentioning

confidence: 99%

Targeting steroid hormone receptors for anti‐cancer therapy—A review on small molecules and nanotherapeutic approaches

Mahadik

Bhattacharya

Padmanabhan

et al. 2021

WIREs Nanomed Nanobiotechnol

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The steroid hormone receptors (SHRs) among nuclear hormone receptors (NHRs) are steroid ligand-dependent transcription factors that play important roles in the regulation of transcription of genes promoted via hormone responsive elements in our genome. Aberrant expression patterns and contextspecific regulation of these receptors in cancer, have been routinely reported by multiple research groups. These gave an window of opportunity to target those receptors in the context of developing novel, targeted anticancer therapeutics. Besides the development of a plethora of SHR-targeting synthetic ligands and the availability of their natural, hormonal ligands, development of many SHR-targeted, anticancer nano-delivery systems and theranostics, especially based on small molecules, have been reported. It is intriguing to realize that these cytoplasmic receptors have become a hot target for cancer selective delivery. This is in spite of the fact that these receptors do not fall in the category of conventional, targetable cell surface bound or transmembrane receptors that enjoy over-expression status. Glucocorticoid receptor (GR) is one such exciting SHR that in spite of it being expressed ubiquitously in all cells, we discovered it to behave differently in cancer cells, thus making it a truly druggable target for treating cancer. This review selectively accumulates the knowledge generated in the field of SHR-targeting as a major focus for cancer treatment with various anticancer small molecules and nanotherapeutics on progesterone receptor, mineralocorticoid receptor, and androgen receptor while selectively emphasizing on GR and estrogen receptor. This review also briefly highlights lipid-modification strategy to convert ligands into SHRtargeted cancer nanotherapeutics.

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Investigating the Role of Mineralocorticoid Receptor Signaling in Cancer Biology in the Genomic Era

Cited by 3 publications

References 91 publications

Steroid hormone receptor based gene delivery systems as potential oral cancer therapeutics

Steroid hormone receptor based gene delivery systems as potential oral cancer therapeutics

AZD9567 versus prednisolone in patients with active rheumatoid arthritis: A phase IIa, randomized, double‐blind, efficacy, and safety study

Targeting steroid hormone receptors for anti‐cancer therapy—A review on small molecules and nanotherapeutic approaches

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