title: Quantitative scoring of differential drug sensitivity for individually optimized anticancer therapies.
abstract: We developed a systematic algorithmic solution for quantitative drug sensitivity scoring (DSS), based on continuous modeling and integration of multiple dose-response relationships in high-throughput compound testing studies. Mathematical model estimation and continuous interpolation makes the scoring approach robust against sources of technical variability and widely applicable to various experimental settings, both in cancer cell line models and primary patient-derived cells. Here, we demonstrate its improved performance over other response parameters especially in a leukemia patient case study, where differential DSS between patient and control cells enabled identification of both cancer-selective drugs and drug-sensitive patient sub-groups, as well as dynamic monitoring of the response patterns and oncogenic driver signals during cancer progression and relapse in individual patient cells ex vivo. An open-source and easily extendable implementation of the DSS calculation is made freely available to support its tailored application to translating drug sensitivity testing results into clinically actionable treatment options.
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
authors.forename: Bhagwan
authors.initials: B
authors.lastname: Yadav
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
authors.forename: Tea
authors.initials: T
authors.lastname: Pemovska
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Szwajda
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Kulesskiy
authors.affiliation: Hematology Research Unit, Helsinki University Central Hospital (HUCH), Helsinki, Finland.
authors.forename: Mika
authors.initials: M
authors.lastname: Kontro
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
authors.forename: Riikka
authors.initials: R
authors.lastname: Karjalainen
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
authors.forename: Muntasir Mamun
authors.initials: MM
authors.lastname: Majumder
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
authors.forename: Disha
authors.initials: D
authors.lastname: Malani
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
authors.forename: Astrid
authors.initials: A
authors.lastname: Murumägi
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Knowles
authors.affiliation: Hematology Research Unit, Helsinki University Central Hospital (HUCH), Helsinki, Finland.
authors.forename: Kimmo
authors.initials: K
authors.lastname: Porkka
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
authors.forename: Caroline
authors.initials: C
authors.lastname: Heckman
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Kallioniemi
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
authors.forename: Krister
authors.initials: K
authors.lastname: Wennerberg
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
authors.forename: Tero
authors.initials: T
authors.lastname: Aittokallio
mesh_terms: D000465:Algorithms; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016022:Case-Control Studies; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008962:Models, Theoretical; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D057285:Precision Medicine; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents