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

Abstract

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.

Design and Characterisation of pH-Responsive Photosensitiser-Loaded Nano-Transfersomes for Enhanced Photodynamic Therapy

“…Cancer is one of the greatest health concerns worldwide [1,2]. Cancer is a devastating disease that results from uncontrollable growth of cells and their subsequent spread across the body [3][4][5]. Currently, various therapeutic strategies for cancer, such as surgery, radiotherapy, and chemotherapy, which can be used either alone or in combination with each other, are available [5].…”

“…Cancer is a devastating disease that results from uncontrollable growth of cells and their subsequent spread across the body [3][4][5]. Currently, various therapeutic strategies for cancer, such as surgery, radiotherapy, and chemotherapy, which can be used either alone or in combination with each other, are available [5]. Chemotherapy, a commonly used anti-cancer strategy, has been developed by screening for natural or synthetic anti-cancer compounds [4,6].…”

“…Chemotherapy, a commonly used anti-cancer strategy, has been developed by screening for natural or synthetic anti-cancer compounds [4,6]. However, traditional chemotherapeutics have drawbacks, such as quick clearance, low drug tolerance due to non-specific biodistribution, and the emergence of drug resistance [3,5,7].…”

pH-Responsive Nano-transferosomes of Purpurin-18 Sodium Salt and Doxorubicin for Enhanced Anticancer Efficiency by Photodynamic and Chemo Combination Therapy

“…Many diseases and activities, such as gene mutations, protein misfolding, and cell malfunction, are attributed to abnormal biological processes at the molecular level . Cancer is a destructive disorder caused by the unstoppable cell growth, which is triggered by a series of genome mutations and their subsequent propagation throughout the body. − Currently, conventional treatments, including surgery, radiotherapy, targeted therapy, and immunotherapy, are administered alone or in combination . Combination therapy is an efficient strategy for improving efficiency and reducing side effects associated with individual use …”

“… 2 − 4 Currently, conventional treatments, including surgery, radiotherapy, targeted therapy, and immunotherapy, are administered alone or in combination. 4 Combination therapy is an efficient strategy for improving efficiency and reducing side effects associated with individual use. 5 …”