2^nd Glycobiology World Congress

Biography

Biography: Nahid Razi

Abstract

Personalized chemotherapy is an unmet need in cancer treatments. A molecular test that can accurately predict the drug efficacy on a patient would be invaluable in selecting effective treatment strategy. We have identified two glycan structures, namely Glycomarker-1 and Glycomarker-2, whose expression levels on the cancer cell surface are associated with responses to chemotherapy with platinum drugs (US patent #7585503, and International pending patent). This finding introduces a new concept, linking glycan cell surface expressions with drug reactivity, and proposes a glycan-mediated mechanism for drug uptake. Our initial studies profiling the cell surface glycans, using Flow Cytometry with specific glycan-binding lectins, on three isogenic pairs of ovarian carcinoma cell-lines, consisting of chemosensitive and acquired chemoresistant phenotypes, revealed at least a ten-fold decrease in alpha2-6Sialyl-R motif (Glycomarker-1) on resistant phenotypes compared to sensitive cells. Further studies by fluorescent confocal microscopy, colony forming assay, sialidase treatments, and mass-spectrometry confirmed the association of Glycomarker-1 with drug uptake. Using Lectin histochemistry (LHC) on clinical samples proved a feasible assay for Glycomarker-1, tested on 64 human ovarian normal and cancerous tissue sections. The LHC on retrospective ovarian cancer specimens, with a known history of drug-response, correctly predicted drug-responses in 22 out of 27 (81.4%) patients. During the studies on the mechanism for drug response, another glycan structure, Glycomarker 2, was identified demonstrating a similar expression pattern to Glycomarker 1. Further studies on Glycomarker-2 suggest an association of the two glycomarkers that would put forward a glycan-mediated mechanism for platinum-drug uptake by cancer cells.