Drug sensitivity and resistance testing (DSRT), established at the Institute for Molecular Medicine Finland (FIMM), University of Helsinki, is a high-throughput assay for testing a large number of therapeutic compounds in a single experiment.
The current compound panel contains more than 500 substances in 5 concentrations and is composed of both approved and investigational drugs. The standard readout includes cell viability (CellTiter-Glo) and cell death (CellTox Green), however, microscopic and flow cytometry-based readouts are also used for more tailored assays. DSRT can be used to give insights on tailored treatment options and to facilitate drug development.
Watch the video below and learn more about the drug sensitivity and resistance testing platform from FIMM experts Heidi Virtanen, Scientific Project Manager, and Jani Saarela, Operational Manager.
One of the first applications of the DSRT was to use it to study ex vivo patient samples obtained from patients suffering from acute myeloid leukemia (AML). These studies were conducted in close collaboration with hematologists working at the Helsinki University Central Hospital (HUCH). To tackle the problem that very little progress had been achieved in developing new treatment options for AML, a large research group composed of hematologists from HUCH and researchers from FIMM, used next-generation sequencing approaches together with DSRT to identify key driver mutations and actionable drug sensitivities.
“One of the biggest challenges is how to identify patients who would benefit from targeted treatments. In our study, one third of the patients showed clinical response to the given tailored targeted treatment. We still need to explore further the associations between genomic and functional information”, explains Mika Kontro, MD, PhD, one of the key hematologists involved in the studies.
“Understanding the complex connections between individual mutations and drug sensitivities helps to identify the patients that would benefit from tailored treatment options and to design optimal drug combinations to treat them”.
“Biobanks that store sample collections and the associated clinical information, provide better means to explore how hematological diseases evolve, and to develop diagnostics and therapeutic options to treat them. The Finnish Hematology Registry and Clinical Biobank (FHRB) collects samples from hematological diseases at the time of diagnosis, at remission and later at relapse if the disease reoccurs. Such high-quality biobank samples can be used to facilitate the development of targeted therapies”, Mika Kontro concludes.
Pemovska T, Kontro M, Yadav B et al., Individualized systems medicine strategy to tailor treatments for patients with chemorefractory acute myeloid leukemia. Cancer Discovery, 3(12):1416-1429, 2013.
Pemovska T, Johnson E, Kontro M et al., Axitinib effectively inhibits BCR-ABL1(T315I) with a distinct binding conformation. Nature, 519:102–105, 2015.