Using QSP to predict cardiotoxicity caused by cancer drugs
Eric Sobie, PhD
Professor, Pharmacological Sciences at
Icahn School of Medicine at Mount Sinai, NY
Wednesday November 18, 2020, 12:00 to 1:00 pm EDT
Register for free at https://www.rosaandco.com/webinars
Abstract:
Tyrosine kinase inhibitor drugs, or TKIs, have been highly effective at
treating several types of cancer, yet many TKIs are associated with various
forms of cardiotoxicity. The mechanisms underlying these drug-induced adverse
events remain poorly understood.
We are exploring potential mechanisms of TKI-induced cardiotoxicity using a
strategy that integrates several complementary approaches. The pipeline
involves: (1) transcriptomics to quantify drug-induced changes in gene
expression in stem cell-derived myocytes (iPSC-CMs); (2) mechanistic QSP
modeling to predict subsequent changes in physiological dynamics; and (3)
physiological measurements to confirm or refute model predictions. This QSP
approach successfully predicted individual-specific TKI susceptibility whereby
particular drugs were tolerated in one cell line but disrupted dynamics in
another cell line.
Overall, the work offers new insight into cardiotoxicity caused by TKIs and
illustrates a novel approach for integrating transcriptomic measurements and
QSP models to generate experimentally testable, individual-specific predictions.