YALE Jo Ur NAL o F BIo Lo GY AND mEDIc INE 85 (2012), pp.29-35. c opyright © 2012. Fo c US: Tr ANSLATIo NAL mEDIc INE pHLIP and Acidity as a Universal Biomarker for Cancer Justin Fendosa* and Donald Engelmanb aDepartment of Biotechnology, Dongseo University, South Korea; bYale University, Department of Molecular Biophysics & Biochemistry, New Haven, Connecticut o f great importance to clinical cancer diagnosis is the use of organic biomarkers. The de- tection of r NA, DNA, and protein antigen are all established methods for identifying specific cancer types and instrumental in promoting greater survivorship of the patient. Despite many decades of intense cancer research, we have yet to identify a “universal” protein or nucleic acid that allows us to diagnose more than a small subset of cancers at a time. In this review, we examine the use of localized cellular acidity as a universal marker for solid tumors, out- lining some successes with a small peptide we call pHLIP, a pH-sensitive biosensor that al- lows us to label tumor tissue in live mice. One of the major forefronts in cancer re- search is the use of biomarkers for cancer di- agnosis. Many methods have been devised in the last two decades to screen protein anti- gen and nucleic acid markers known to be specific to different tumor types [1]. Perhaps the most successful in this line of biomarker technologies has been the development of as- says sensitive to changes in Her2/Neu ex- pression, the aggressive breast tumor proto-oncogene [2]. Protein and RNA ex- pression assays have been in use clinically for some time, and the recent advent of DNA-based techniques allows clinicians the opportunity to monitor specific mutations over time by tracking susceptible genes in patients with established genetic risk [3]. Al- though these methods are crucial for the early detection of disease, they are all limited by the fact that each method detects only one or, *To whom all correspondence should be addressed: Justin Fendos, Department of Biotechnology, Dongseo University, 47 Jurye-ro Sasang-gu, Busan 617-716, South Korea; Tele: 82-51-320-2662; Fax: 82-51-320-2094; Email: justin.fendos@yale.edu. †Abbreviations: pHLIP, pH-Low Insertion Peptide; PNA, peptide nucleic acid. Keywords: cancer, pHLIP, diagnosis, biosensor, biomarker, pH, inflammation, arthritis, cell translocation 29