BioCentury
ARTICLE | Distillery Techniques

Assays and screens; biomarkers

November 6, 2018 7:45 PM UTC

Gene profiling coupled with cell-based assays of patient samples could help predict drug responses in AML patients. In tumor samples from 363 patients, whole-exome sequencing plus genotyping of nucleophosmin (NPM1; B23) and FMS-like tyrosine kinase 3 (FLT3; CD135) followed by primary cell-based drug response assays identified multiple associations between gene mutations and responses to 122 drugs. These included sensitivity to phosphoinositide 3-kinase (PI3K) inhibitors in tumors harboring runt-related transcription factor 1 (RUNX1) mutations; resistance to Zelboraf vemurafenib in tumors harboring neuroblastoma Ras viral oncogene (NRAS) mutations; and sensitivity to Imbruvica ibrutinib in tumors harboring FLT3 mutations alone or in combination with NPM1 mutations. Also in the patient samples, RNA sequencing and the drug response assay identified associations between gene expression patterns and response to 78 of the 122 drugs, including a 17-gene signature comprising CD86 (B7-2) and 10 other genes for which high expression was associated with Imbruvica resistance, and microRNA-223 (miR-223) and five additional genes for which high expression was associated with Imbruvica sensitivity. Next steps include testing the assay’s ability to predict patient outcomes in AML.

AbbVie Inc. markets Imbruvica, a Bruton’s tyrosine kinase (Btk) inhibitor, for graft-versus-host disease (GvHD), non-Hodgkin lymphoma (NHL), mantle cell lymphoma (MCL), small lymphocytic lymphoma (SLL) and chronic lymphocytic leukemia (CLL)...