Paul Tempst
Memorial Sloan Kettering Cancer Center, USA
Title: Aminopeptidase activities as biomarkers for cancer
Biography
Biography: Paul Tempst
Abstract
Human cells produce 550 proteases with widely different functions. Several have been implicated in cancer where they promote both tumor progression and suppression. Our group has discovered exopeptidase activities in previous onco-peptidomic studies that provided class discrimination between patients with different types of solid tumors. Owing to their relatively low levels in serum on an immense proteome background, exopeptidases have rarely been detected in proteomic screens and therefore not evaluated as potential biomarkers. Our cancer biomarker discovery studies have therefore focused on proteolytic activities as opposed to steady state levels. We have developed fluorescence-based, quantitative assays to selectively measure activities of 10 individual aminopeptidases (APs) in blood serum or plasma without the need for any sample pre-fractionation or pre-treatment. These tests are uniquely suited to probe altered AP activities in cancer patients and can be applied in parallel to analyze large numbers of samples, followed by multivariate statistical analysis. So far, we have discovered a 2-plex AP activity pattern that allowed prediction of breast cancer biopsy outcome (malignant or benign) with good sensitivity and specificity, as well as a 2-plex pattern that correlates well with high risk (i.e., short survival) of patients with castrate resistant metastatic prostate cancer. Future studies will focus on development and large-scale screens of aminopeptidase and other protease activity assays as markers in a variety of tumor types. If effective functional cancer biomarker panels materialize, it would have a major clinical impact for non-invasive cancer detection and prognostication.