GlycoMimetics, Inc.
METHODS FOR USE OF GENE EXPRESSION AS AN INDICATOR OF E-SELECTIN INHIBITOR EFFICACY AND CLINICAL OUTCOME FOR MULTIPLE TUMOR TYPES

Abstract:

Cancer patients that express high levels of the E-selectin ligand (sialyl Le.sup.a/x) on their tumors have a poorer outcome. Interestingly, relapsed/refractory acute myeloid leukemia (AML) patients expressing high levels of sialyl Le.sup.x on their blasts show the greatest therapeutic response when treated with the E-selection inhibitor compound of Formula I. Transcriptome profiling of E-selectin ligand-forming glycosylation genes showed that ST3GAL4 and FUT7 were consistently expressed in the majority of cancers evaluated. Poor survival outcomes of FLT3-mutated AML patients that express high levels of ST3GAL4 and FUT7 implicated E-selectin in this disease state. These genes may be predictive biomarkers in AML patients. Methods of treatment of cancer comprising screening AML patients for expression of genes that contribute to the synthesis of the E-selectin ligand sialyl Le.sup.x, then treating those patients with an E-selection inhibitor, are disclosed.