2. Academic Validation
  3. Standardized assays to monitor drug sensitivity in hematologic cancers

Standardized assays to monitor drug sensitivity in hematologic cancers

  • Cell Death Discov. 2023 Dec 1;9(1):435. doi: 10.1038/s41420-023-01722-5.
Pilar Ayuda-Durán 1 2,  Johanne U Hermansen 3 4,  Mariaserena Giliberto 3 4,  Yanping Yin 3 4 5,  Robert Hanes 1 2 6,  Sandra Gordon 7,  Heikki Kuusanmäki 7 8,  Andrea M Brodersen 1 2 6,  Aram N Andersen 1 2 6,  Kjetil Taskén 3 4,  Krister Wennerberg 7,  Jorrit M Enserink 1 2 6,  Sigrid S Skånland 9 10
Affiliations

Affiliations

  • 1 Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
  • 2 Centre for Cancer Cell Reprogramming, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
  • 3 Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
  • 4 K. G. Jebsen Centre for B Cell Malignancies, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
  • 5 Department of Haematology, Oslo University Hospital, Oslo, Norway.
  • 6 Section for Biochemistry and Molecular Biology, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway.
  • 7 Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
  • 8 Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.
  • 9 Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway. sigrid.skanland@ous-research.no.
  • 10 K. G. Jebsen Centre for B Cell Malignancies, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. sigrid.skanland@ous-research.no.
PMID: 38040674 DOI: 10.1038/s41420-023-01722-5
Abstract

The principle of drug sensitivity testing is to expose Cancer cells to a library of different drugs and measure its effects on cell viability. Recent technological advances, continuous approval of targeted therapies, and improved Cell Culture protocols have enhanced the precision and clinical relevance of such screens. Indeed, drug sensitivity testing has proven diagnostically valuable for patients with advanced hematologic cancers. However, different cell types behave differently in culture and therefore require optimized drug screening protocols to ensure that their ex vivo drug sensitivity accurately reflects in vivo drug responses. For example, primary chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) cells require unique microenvironmental stimuli to survive in culture, while this is less the case for acute myeloid leukemia (AML) cells. Here, we present our optimized and validated protocols for culturing and drug screening of primary cells from AML, CLL, and MM patients, and a generic protocol for cell line models. We also discuss drug library designs, reproducibility, and quality controls. We envision that these protocols may serve as community guidelines for the use and interpretation of assays to monitor drug sensitivity in hematologic cancers and thus contribute to standardization. The read-outs may provide insight into tumor biology, identify or confirm treatment resistance and sensitivity in real time, and ultimately guide clinical decision-making.

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