Abstract

TME-Friendly Microfluidic Platforms for High-Fidelity Cancer Drug Testing

Albert Folch, Professor of Bioengineering, University of Washington

There is a lack of confidence in present in vitro drug efficacy tests, as they do not properly recapitulate the dynamic physiology and pathophysiology of the human organism. This challenge is particularly acute in oncology: present tools to study drug responses fail to faithfully mimic the patient’s tumor microenvironment (TME) and thus have not kept up with drug testing needs. As a measure of this problem, on average less than 4% of oncology drugs in clinical trials end up being FDA-approved, a dismal approval rate that has dire social repercussions such as high cancer drug prices and difficult accessibility. We have developed a suite of microfluidic platforms that address this problem by multiplexing the delivery of drugs to intact-TME human biopsies, altogether bypassing animal testing. The first of these platforms (called OncoSlice) allows for delivering drugs to live tumor slices. We have demonstrated the use of Oncoslice for the delivery of small-molecule cancer drug panels to xenograft slices as well as to slices from patient solid tumors (GBM and colorectal liver metastasis). In addition, we have developed a precision slicing methodology that allows for producing large numbers of cuboidal micro-tissues (“cuboids”) from a single tumor biopsy. We have been able to trap cuboids in arrays of microfluidic traps in a 96-well platform and we are exploring robotics for very high-throughput automated placement of mouse cuboids in 384-well plates. We believe that with these approaches it will soon be possible to bypass animal testing and perform direct testing of drugs using only human tumors. Since these new-generation tests preserve the TME intact, we envision that they will minimize FDA failure rates and could contribute to alleviate the cost of cancer drugs.