Engineering a Rational Approach to Precision Oncology Drugs

Clinical trials of new oncology drugs have a staggering 97% failure rate typically due to toxicity or lack of drug efficacy.  One common issue is failure to understand the mechanism of action and misidentification of putative biomarkers indicative of drug response.  To address this issue, we have developed and clinically deployed an innovative implantable microdevice (called the Nanonail^TM) for functional and simultaneous intra tumormolecular profiling of tumor sensitivity to up to 20 different oncology drugs and/or drug combinations per microdevice at the single cell level and with the tumor in its native microenvironment.  Each unique drug or drug combination is loaded into one of the micromachined depots of the Nanonail for delivery of a controlled dose of drug to the surrounding tumor tissue once inserted into the tumor with a standard fine needle biopsy tool. After 1-3 days the device is recovered with a plug of surrounding tissue and processed according to standard histopathology protocols.  Thin sections of the zone of drug-tumor interaction are individually analyzed to create a detailed, high resolution spatial multi-omic profile of the tumor response to each agent.  An additional benefit, molecular profiling the tumor-drug response along the spatial diffusion profile of drug from each depot provides key information on tumor response to different drug doses. We will provide examples on how application of single cell functional profiling can reveal novel, potent anti-tumor drug combinations and in particular the combination of an immunotherapy with molecularly targeted or cytotoxic agents.