Ex vivo drug response profiling detects recurrent sensitivity patterns in drug-resistant acute lymphoblastic leukemia

著者: Viktoras Frismantas, Maria Pamela Dobay, Anna Maria Rinaldi, Joëlle Tchinda, Samuel H. Dunn, Joachim B. Kunz, Paulina Richter‐Pechańska, Blerim Marovca, Orrin Pail, Silvia Jenni, Ernesto Díaz-Flores, Bill H. Chang, Timothy J. Brown, Robert H. Collins, Sebastian Uhrig, Gnana Prakash Balasubramanian, Obul Reddy Bandapalli, Salome Higi, Sabrina Eugster, P. Voegeli, Mauro Delorenzi, Gunnar Cario, Mignon L. Loh, Martin Schrappe, Martin Stanulla, Andreas E. Kulozik, Martina U. Muckenthaler, Vaskar Saha, Julie Irving, Roland Meisel, Thomas Radimerski, Arend von Stackelberg, Cornelia Eckert, Jeffrey Tyner, Péter Horváth, Beat Bornhäuser, Jean‐Pierre Bourquin - Blood 2017 被引用: 260

ALL, and in some T-cell ALLs (T-ALLs), predicting in vivo activity as a single agent and in combination with dexamethasone and vincristine. Unexpected sensitivity to dasatinib with half maximal inhibitory concentration values below 20 nM was detected in 2 independent T-ALL cohorts, which correlated with similar cytotoxic activity of the SRC inhibitor KX2-391 and inhibition of SRC phosphorylation. A patient with refractory T-ALL was treated with dasatinib on the basis of drug profiling information and achieved a 5-month remission. Thus, drug profiling captures disease-relevant features and unexpected sensitivity to relevant drugs, which warrants further exploration of this functional assay in the context of clinical trials to develop drug repurposing strategies for patients with urgent medical needs.