Seahorse Bioscience, a part of Agilent Technologies and the leader in metabolic analyzers and assay kits for measuring cell metabolism, has reached its 500th citation in cancer research. Published in Scientific Reports, the paper hypothesizes that because aberrant activation of the PI3K/Akt/mTOR pathway is a common feature of acute myeloid leukemia (AML) patients, contributing to chemoresistance, disease progression and unfavorable outcome, the inhibition of this pathway may represent a potential therapeutic approach in AML.
The study evaluated the in vitro activity of NVP-BKM120 (BKM120), a selective pan-class I PI3K inhibitor on AML cells. Titled The pan-class I phosphatidyl-inositol-3 kinase inhibitor NVP-BKM120 demonstrates anti-leukemic activity in acute myeloid leukemia, the publication is based on research carried out in the Cell Kinetics and Applied Proteomics Lab, Department of Clinical and Molecular Medicine at the Sapienza University of Rome, including collaborations with the university's Department of Cellular Biotechnologies and Haematology; the Division of Clinical Haematology-Oncology at the European Institute of Oncology in Milan; and the Department of Haematology at the Tor Vergata University Hospital in Rome.
"Based on our ongoing translational research on leukemia, and more broadly, on neoplastic malignancies, we have been moving from targeting oncogene-driven aberrant signaling pathways to a novel approach based on combinations of molecules that deactivate the aberrant signaling with drugs aimed at impairing leukemia cell metabolism. We believe this two-level intervention can improve the therapeutic efficacy," stated the paper's lead author, Agostino Tafuri, associate professor of Haematology, Department of Clinical and Molecular Medicine, Sapienza University and Sant'Andrea Hospital of Rome.
"This innovative approach has been successfully explored through the use of the Seahorse XF Extracellular Flux Analyzer, which proved to be the appropriate methodology for dissecting the real metabolic status of leukemia cells," Tafuri said. "Furthermore, using the XF Analyzer we were able to track the metabolic changes induced by these molecules, which eventually resulted in leukemia cell death, prompting further clinical investigations. This research approach will broaden to include other hematological malignancies, including lymphomas, myeloma, lympho- and myelo-proliferative diseases, to also evaluate the metabolic phenotype of these diseases and assess the activity of metabolic targeting molecules."
Seahorse XF technology was integral to revealing the effects of BKM120 on the metabolic phenotype of AML cells. Given the roles of the PI3K/Akt/mTOR pathways in cell metabolism, the authors evaluated BKM120 on both mitochondrial respiration and glycolysis, the two major energy pathways of the cell. By examining the metabolic signatures, the authors demonstrated that the significant decrease in cellular metabolism in both continuous and primary AML cells is indicative of the efficacy of this compound in AML cells. These findings support the further clinical assessment of this compound in the treatment of AML.
Seahorse XF technology has established standards for measuring cell metabolism via its ability to deliver meaningful new parameters for understanding the processes by which cells produce and consume energy. This is done via the simultaneous measurement of the two major energy-producing pathways within the cell - mitochondrial respiration and glycolysis - in live cells, in real time. This knowledge is increasingly helping scientists to understand better the connection between cellular physiological traits with genomic and proteomic data. It is generating new insights into disease and new ideas into disease treatment and therapy.