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Tuesday, October 22 • 2:10pm - 2:30pm
Complex Translational Models-Development of Advanced Models of Haematopoiesis and their Application to Cancer Therapeutics

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Haematological toxicity is a common safety challenge for many monotherapy and combination cancer therapies which can result in dose reductions and discontinuation to the point where the drugs become ineffective. To address the challenge, we are developing advanced in vitro models using primary human CD34+ hematopoietic stem and progenitor cells (HSPC’s) to assess drug induced haematological toxicity. Our aim is to provide human relevant in vitro data to inform on monotherapy and combination bone marrow risk and to optimise rational drug combination choices and scheduling in the clinic. Recent advances in 2D and 3D microphysiological systems (organ-on-a-chip) have opened new possibilities to investigate different aspects of haematological toxicity. Using CD-marker profiling we have defined the differentiation kinetics of HSPCs to either erythroid, myeloid, or megakaryocytic lineages. 2D systems allow a high throughput assessment of monotherapy or combinations risk whilst 3D system with continuous stem cell re-population and assay longevity also allows the capability to assess recovery and dose scheduling. The initial validation of these systems is very encouraging and appears to closely resemble the lineage specific hematological toxicity observed clinically.

Speakers
avatar for Mark Anderton, Ph.D.

Mark Anderton, Ph.D.

Director of Drug Safety, AstraZeneca
Mark Anderton is a Director of drug safety within the Oncology Safety department of AstraZeneca. He earned his PhD in Cancer Pharmacology and Toxicology at the MRC Toxicology Unit, Leicester. After his PhD, Mark joined Vertex Pharmaceuticals, UK where he gained experience in all... Read More →

Chair
TS

Timothy Spicer, BS, MS, Ph.D.

Senior Scientific Director, Scripps Research Florida


Tuesday October 22, 2019 2:10pm - 2:30pm
Wellcome Auditorium