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World J Gastroenterol. Nov 14, 2012; 18(42): 6027-6035
Published online Nov 14, 2012. doi: 10.3748/wjg.v18.i42.6027
Human endogenous retroviruses and cancer: Causality and therapeutic possibilities
Christina S Mullins, Michael Linnebacher
Christina S Mullins, Michael Linnebacher, Department of General, Thoracic, Vascular and Transplantation Surgery, Section Molecular Oncology and Immunotherapy, University of Rostock, Schillingallee 35, 18057 Rostock, Germany
Author contributions: Mullins CS and Linnebacher M analyzed the literature and wrote the paper.
Supported by Grants from the State Mecklenburg-Vorpommern and from Deutsche Krebshilfe, No. 108446
Correspondence to: Michael Linnebacher, PhD, Department of General, Thoracic, Vascular and Transplantation Surgery, Section Molecular Oncology and Immunotherapy, University of Rostock, Schillingallee 35, 18057 Rostock, Germany. michael.linnebacher@med.uni-rostock.de
Telephone: +49-381-4996043 Fax: +49-381-4996002
Received: June 5, 2012
Revised: September 10, 2012
Accepted: September 19, 2012
Published online: November 14, 2012
Abstract

A substantial part of the human genome is derived from transposable elements; remnants of ancient retroviral infections. Conservative estimates set the percentage of human endogenous retroviruses (HERVs) in the genome at 8%. For the most part, the interplay between mutations, epigenetic mechanisms and posttranscriptional regulations silence HERVs in somatic cells. We first highlight mechanisms by which activation of members of several HERV families may be associated with tumor development before discussing the arising chances for both diagnosis and therapy. It has been shown that at least in some cases, tumor cells expressing HERV open reading frames (ORFs) thus gain tumor-promoting functions. However, since these proteins are not expressed in healthy tissues, they become prime target structures. Of potential pharmacological interest are the prevention of HERV transposition, the inhibition of HERV-encoded protein expression and the interference with these proteins’ activities. Evidence from recent studies unequivocally proves that HERV ORFs represent a very interesting source of novel tumor-specific antigens with even the potential to surpass entity boundaries. The development of new tumor (immune-) therapies is a very active field and true tumor-specific targets are of outstanding interest since they minimize the risk of autoimmunity and could reduce side effects. Finally, we postulate on main future research streams in order to stimulate discussion on this hot topic.

Keywords: Human endogenous retroviruses; Gastrointestinal cancer; Therapeutic targets; Tumor-specific antigens; Tumorigenesis