The Investigative Toxicology Laboratory develops and implements mechanism-based in vitro models to identify potential liabilities and investigates mechanisms of various targeted organ toxicities in support of programs within the National Cancer Institute's Division of Cancer Treatment and Diagnosis

Investigating cellular toxicities for informed anticancer drug development 

We investigate adverse effects from anticancer drugs to support the National Cancer Institute’s Toxicology and Pharmacology Branch, helping inform NCI’s Developmental Therapeutics Program. We contribute to in vitro strategies to investigate cellular toxicities that complement the program’s mission to discover, develop, and characterize new anticancer drugs and their molecular targets.  

Cutting-edge technology for improved organ toxicity assessments 

We develop and implement mechanism-based, human-relevant in vitro assays with leading-edge technology to improve and apply the translational accuracy and predictive power of organ toxicity assessments for the early discovery and development of new anticancer agents. We screen for compounds that effectively prevent or reverse organ toxicity caused by anticancer agents.  

CAR T-cell therapy evaluation 

We use an in vitro assay to evaluate on- or off-target and/or off-tumor toxicities of cell-based cancer therapies aimed at specific cancer targets through genetically modified receptors. Various types of human induced pluripotent stem cells are used as models of “normal” target cells. These studies are used to support safety assessments of cell-based therapies prior to first-in-human clinical trials. 

Additional Content
  • In vitro on- or off-target/off-tumor screening  

  • Assessment of potential toxicities of CAR T-cell therapies  

  • Use of human induced pluripotent stem cells as “normal” target cells  

  • Support for non-clinical safety assessments prior to first-in-human studies for CAR T-cell therapies 

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Comprehensive in vitro proarrhythmia assay 

We evaluate various cancer therapies for potential cardiotoxicity. This assay uses human induced pluripotent stem cell cardiomyocytes as an in vitro model for cardiac muscle cells and can be used to support safety assessments of different cancer treatments prior to first-in-human studies. 

Additional Content
  • Improved strategy for assessment of cardiotoxicity of various cancer treatments  

  • Focused on predicting torsadogenic hazard over hERG inhibition and QT prolongation 

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Chemotherapy-induced peripheral neuropathy assay 

We evaluate various drugs that might prevent or repair the peripheral nerve damage that can be a debilitating side effect of some chemotherapy-based cancer treatments. This assay uses human induced pluripotent stem cell peripheral nerves as a model for normal human peripheral nerves. 

Additional Content
  • Established and qualified in vitro human peripheral nervous system model for chemotherapy-induced peripheral neuropathy assay screening  

  • Use of human induced pluripotent stem cells as a model of “normal” peripheral nerves  

  • Assessment used to screen therapies for potential to prevent or repair peripheral nerve toxicity