HISTOLOGY AND HISTOPATHOLOGY

Cellular and Molecular Biology

 

Review

An update on the pathobiological relevance of nuclear receptors for cancers of the head and neck

Roland H. Stauber1, Desiree Wünsch1, Shirley K. Knauer2 and Verena Fetz1

1Molecular and Cellular Oncology, University Hospital of Mainz, Mainz, Germany and 2Institute for Molecular Biology, Centre for Medical Biotechnology (ZMB), University Duisburg-Essen, Universitätsstraße, Essen, Germany.

Offprint requests to: R.H. Stauber or V. Fetz, Molecular and Cellular Oncology, University Hospital of Mainz, Lagenbeckstrasse 1, 55101, Mainz, Germany. e-mail: rstauber@uni-mainz.de or fetzv@uni-mainz.de


Summary. Cancers of the head and neck are among the most common neoplasms worldwide, characterized by local tumor aggressiveness, high rate of early recurrence, development of metastasis and second primary tumors. Although disease management of head and neck cancer has improved significantly, overall survival-rates remained largely unchanged over the last decades. Thus, in addition to modern chemo-radiation treatment strategies combined with sophisticated surgery, there is still a need for molecular markers and key regulatory factors exploitable for chemoprevention and targeted therapies.
A critical event in carcinogenesis is the uncontrolled modulation of genetic programs, mediated by deregulated signaling cascades, together with downstream transcriptional modulators. Hence, nuclear receptors, belonging to a superfamily of transcription factors implicated in a broad spectrum of physiological and pathophysiological processes, have also been associated with HNC. Enhanced expression of several nuclear receptors has been shown in head and neck cancer cells, and strategies targeting these molecules have been developed and tested in the clinics. In particular, the effects of retinoids targeting nuclear receptors of the thyroid hormone receptor-like receptor subfamily have been vigorously examined in large clinical chemoprevention trials.
This review seeks to provide a general overview of nuclear receptors’ molecular functions and summarizes their prognostic/therapeutic relevance, as well as the (pre)clinical studies targeting nuclear receptors in HNC
. Histol Histopathol 25, 1093-1104 (2010)

Key words: Chemoprevention, Chemotherapy, Hormone response element, PPAR, RAR, Retinoids, RXR, Squamous cell carcinoma, Tamoxifen, Transcriptional activation

DOI: 10.14670/HH-25.1093