Nuclear receptors: recent drug discovery for cancer therapies.

Nuclear receptors: recent drug discovery for cancer therapies. Endocr Rev. 2019 Mar 14;: Authors: Zhao L, Zhou S, Gustafsson JÅ Abstract Nuclear receptors (NRs) are transcription factors actively involved in many aspects of human physiology and pathology, serving as sensors of stimuli, master regulators of downstream molecular events and hubs governing complex gene regulatory networks. The importance of various members of the NR superfamily in cancer has led to substantial efforts to target them therapeutically. Notably, drugs that block the action of estrogen receptor alpha (ERα) in patients with ERα+ breast cancer or the androgen receptor (AR) in prostate cancer patients have provided remarkable improvements in survival. However, there is continuing need for novel drugs that target ERα or AR owing to resistance to established drugs, and there are also promising opportunities for targeting other nuclear receptors in cancer. In this article, we overview NR-based drug discovery in cancer and related resistance mechanisms, focusing on novel strategies for targeting well-established NR targets, including ERα, AR, the glucocorticoid receptor and the progesterone receptor, as well as opportunities to target other NRs that are attracting interest in immuno-oncology, such as liver X receptors (LXRs), RAR-related orphan receptors (RORs) and farnesoid X receptors (FXRs). PMID: 30869771 [PubMed - as supplied by publisher]
Source: Endocrine Reviews - Category: Endocrinology Tags: Endocr Rev Source Type: research

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Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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