Autoantibody signatures: Progress and perspectives for early cancer detection

Abstract

Introduction • Unknown origins of autoantibody production in cancer • The use of proteomics to identify autoantibodies • Clinical utility of autoantibody signatures for early detection of cancer - Autoantibodies as potential cancer biomarkers - Defining autoantibody signatures in cancer: still many challenges • Autoantibody detection to build screening tests in high-risk populations • Conclusion and perspectives Becoming invasive is a crucial step in cancer development, and the early spread of tumour cells is usually undetected by current imaging technologies. In patients with cancer and no signs of overt metastases, sensitive methods have been developed to identify circulating autoantibodies and their antigen counterparts in several cancers. These technologies are often based on proteomic approaches, and recent advances in protein and antibody microarrays have greatly facilitated the discovery of new antibody biomarkers in sera from cancer patients. Interestingly, in a clinical application setting, combinations of multiple autoantibody reactivities into panel assays have recently been proposed as relevant screening tests and validated in several independent trials. In addition, autoantibody signatures seem to be particularly relevant for early detection of cancer in high-risk cancer patients. In this review, we highlight the concept that immunogenic epitopes associated with the humoural response and key pathogenic pathways elicit serum autoantibodies that can be considered as relevant cancer biomarkers. We outline the proteomic strategies employed to identify and validate their use in clinical practice for cancer screening and diagnosis. We particularly emphasize the clinical utility of autoantibody signatures in several cancers. Finally, we discuss the challenges remaining for clinical validation. © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.