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Chip Device Tests for Cancer Drug Efficacy, Toxicity

Multi-organ chip device with five chambers, highlighted in green dye. (Hesperos Inc., Science Translational Medicine)

20 June 2019. A configurable chip device simulating several human organs is shown in lab tests to simultaneously test cancer drugs for both their efficacy and toxicity. A description of the system and test results appear in yesterday’s issue of the journal Science Translational Medicine (paid subscription required).

The chip device is developed by Hesperos Inc., a spin-off enterprise from University of Central Florida, or UCF, both in Orlando, Florida. The company’s microfluidic or lab-on-a-chip systems contain wells and finely-etched channels lined with human tissue cells that work like tissue and cells in human organs, as well as sensors and electronics to measure and report bio-chemical activity. The authors led by Hesperos founder and chief scientist James Hickman, also professor of nano-science at UCF, are seeking better methods to assess new drugs for toxic effects before testing on humans. At present, nearly all new drugs are tested on lab animals that may not adequately represent the full complexity of human organs.

The Hesperos devices contain tissue and cells from multiple organs to test for possible toxicity of new drugs, as well as evaluate their activity against the drugs’ biological targets. The company says its devices are configurable to represent actions of multiple organs with tissue and cell samples from individual patients that test not only for direct effects of the drugs, but also the metabolized end-products of the treatments. With these results, its chip devices offer data to calculate a therapeutic index for the drugs being tested: a ratio of the dose that begins to produce toxic effects, over the dose needed to generate a therapeutic result.

Researchers from Hesperos, with colleagues from UCF and drug maker Roche, tested drugs on two different types of cancer using a device with five chambers configured to represent different organs containing cancer cells and other organs to measure possible toxic effects. In one set of tests, a chip device contained bone marrow cells with leukemia, with which the team tested the cancer drugs diclofenac, a non-steroid anti-inflammatory drug repurposed to treat various types of cancer, and the chemotherapy drug imatinib, known commercially as Gleevec. Results show both drugs able to stop the proliferation of cancer cells in the bone marrow, but diclofenac reduced functioning of liver tissue on the chip by 30 percent, while imatinib had no effect on the liver tissue.

In the second set of tests, the researchers configured the chip to contain breast and drug-resistant vulva tissue with cancer cells, and tested the breast cancer chemotherapy drug tamoxifen, by itself and with verapamil, a drug to treat high blood pressure in a class of treatments called calcium-channel blockers. The Hesperos chip, in this case, contained separate chambers with liver tissue and heart muscle cells derived from stem cells to test for off-target effects.

The results illustrate the sometimes complex interactions of different drugs given at the same time. Tamoxifen, say the authors, worked alone against breast cancer cells, but only after metabolized by the liver tissue, and had no effect on the vulva cancer. When supplemented with verapamil, however, tamoxifen was active against vulva cancer. Moreover, heart muscle cells in the chip remained viable after tamoxifen alone or with verapamil, but showed reduced contracting force, beat frequency, and electrical signaling frequency.

Hesperos takes part in the Tissue Chip for Drug Screening program run by National Center for Advancing Translational Sciences, or NCATS, part of National Institutes of Health. The company says it receives funding through Small Business Innovation Research grants from NCATS.

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