Forskning ved Københavns Universitet - Københavns Universitet

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Quantitative scoring of differential drug sensitivity for individually optimized anticancer therapies

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Bhagwan Yadav
  • Tea Pemovska
  • Agnieszka Szwajda
  • Evgeny Kulesskiy
  • Mika Kontro
  • Riikka Karjalainen
  • Muntasir Mamun Majumder
  • Disha Malani
  • Astrid Murumägi
  • Jonathan Knowles
  • Kimmo Porkka
  • Caroline Heckman
  • Olli Kallioniemi
  • Wennerberg, Krister
  • Tero Aittokallio

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.

OriginalsprogEngelsk
TidsskriftScientific Reports
Vol/bind4
Sider (fra-til)5193
ISSN2045-2322
DOI
StatusUdgivet - 5 jun. 2014
Eksternt udgivetJa

ID: 199429874