Telomerase as Biomarker in Colorectal Cancer

Abstract

Colorectal cancer (CRC) is the third most commonly diagnosed cancer, with over one million new cases every year. Although improved treatments, increased awareness, and early detection have contributed to prolonged survival, CRC still represents an important cause of cancer-related deaths. CRC is a heterogeneous complex of diseases differing in molecular pathways and biological R. Bertorelle Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto, IOV-IRCCS, Padova, Italy e-mail: roberta.bertorelle@unipd.it A. De Rossi (*) Department of Surgery, Oncology and Gastroenterology, Section of Oncology and Immunology, University of Padova, and Istituto Oncologico Veneto, IOV-IRCCS, Padova, Italy Istituto Oncologico Veneto, Padova, Italy e-mail: anita.derossi@unipd.it # Springer Science+Business Media Dordrecht 2015 V.R. Preedy, V.B. Patel (eds.), Biomarkers in Cancer, Biomarkers in Disease: Methods, Discoveries and Applications, DOI 10.1007/978-94-007-7681-4_2 659 characteristics, arising through a multistep process; this molecular and biological heterogeneity also accounts for the great clinical variability of the disease. The management of CRC requires a multimodal approach, and many efforts have been made to identify molecular markers able to predict the outcome of CRC patients. Telomerase is a ribonucleoprotein complex containing the catalytic protein telomerase reverse transcriptase (TERT) with telomere-specific reverse transcriptase activity which synthesizes telomere sequences utilizing an internal RNA template. The maintenance of telomere length by telomerase is critical to preserving the replicative potential of cancer cells. Several pieces of evidence suggest that TERT, besides its capacity to extend telomeres, is also involved in other cellular functions, including activation of proliferative signaling pathways and antiapoptotic activity, even by telomere-length-independent mechanisms. In view of its critical role in the oncogenetic process, telomerase may be a molecular marker of neoplastic disease. The aim of this chapter is to analyze literature data in order to assess the role of telomerase expression and/or activity in the carcinogenesis of colorectal cancer and its value as a prognostic marker of disease progression. The potential use of circulating TERT as a biomarker for minimally invasive monitoring of the disease and response to therapy is also discussed. List of Abbreviations APC Adenomatous Polyposis Coli CIN Chromosomal Instability CRC Colorectal Cancer CRT Chemoradiotherapy DCC Deleted in Colorectal Carcinoma DFS Disease-Free Survival EGFR Epidermal Growth Factor Receptor FU Fluorouracil GAPDH Glyceraldehyde-3-Phosphate Dehydrogenase HIF Hypoxia-Inducible Factor HPRT1 Hypoxanthine Phosphoribosyltransferase 1 MAPK Mitogen-Activated Protein Kinase MMR Mismatch Repair System MSI Microsatellite Instability MSS Microsatellite Stable OS Overall Survival PCR Polymerase Chain Reaction TERT Telomerase Reverse Transcriptase TRAP Telomere Repeat Amplification Protocol 660 R. Bertorelle and A. De Rossi