Orphan nuclear receptors as drug targets for the treatment of prostate and breast cancers.

Abstract

Nuclear receptors (NRs), a family of 48 transcriptional factors, have been studied intensively for their roles in cancer development and progression. The presence of distinctive ligand binding sites capable of interacting with small molecules has made NRs attractive targets for developing cancer therapeutics. In particular, a number of drugs have been developed over the years to target human androgen- and estrogen receptors for the treatment of prostate cancer and breast cancer. In contrast, orphan nuclear receptors (ONRs), which in many cases lack known biological functions or ligands, are still largely under investigated. This review is a summary on ONRs that have been implicated in prostate and breast cancers, specifically retinoic acid-receptor-related orphan receptors (RORs), liver X receptors (LXRs), chicken ovalbumin upstream promoter transcription factors (COUP-TFs), estrogen related receptors (ERRs), nerve growth factor 1B-like receptors, and ‘‘dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1’’ (DAX1). Discovery and development of small molecules that can bind at various functional sites on these ONRs will help determine their biological functions. In addition, these molecules have the potential to act as prototypes for future drug development. Ultimately, the therapeutic value of targeting the ONRs may go well beyond prostate and breast cancers.

• Authors: Mani Roshan-Moniri, Michael Hsing, Miriam S Butler, Artem Cherkasov, Paul S Rennie
• Journal: Cancer treatment reviews (Cancer Treat Rev) Vol. 40 Issue 10 Pg. 1137-52 (Dec 2014) ISSN: 1532-1967 [Electronic] Netherlands
• PMID: 25455729 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antineoplastic Agents
• COUP Transcription Factor I
• COUP Transcription Factors
• DAX-1 Orphan Nuclear Receptor
• Liver X Receptors
• Membrane Transport Proteins
• NR0B1 protein, human
• NR2F1 protein, human
• NR4A2 protein, human
• Nuclear Receptor Subfamily 1, Group F, Member 1
• Nuclear Receptor Subfamily 4, Group A, Member 2
• OSCP1 protein, human
• Orphan Nuclear Receptors
• RORA protein, human
• Small Molecule Libraries

Topics

• Antineoplastic Agents (pharmacology)
• Breast Neoplasms (drug therapy, metabolism)
• COUP Transcription Factor I (metabolism)
• COUP Transcription Factors (metabolism)
• DAX-1 Orphan Nuclear Receptor (metabolism)
• Female
• Humans
• Liver X Receptors
• Male
• Membrane Transport Proteins (metabolism)
• Molecular Targeted Therapy (methods)
• Nuclear Receptor Subfamily 1, Group F, Member 1 (metabolism)
• Nuclear Receptor Subfamily 4, Group A, Member 2 (metabolism)
• Orphan Nuclear Receptors (metabolism)
• Prostatic Neoplasms (drug therapy, metabolism)
• Small Molecule Libraries (pharmacology)