An implantable microdevice to perform high-throughput in vivo drug sensitivity testing in tumors

An implantable microdevice is demonstrated to release microdoses of multiple drugs into confined regions of tumors and allows for assessment of each drug’s efficacy to identify optimal therapy. Drug-releasing implant tests cancer’s resolve Predicting whether a patient will respond to a drug is not easy, often relying on empirical evidence. Toward personalized medicine, animal models of patient tumors have been developed as well as engineered cell-material combinations meant to replicate a tumor in vitro. But the true test of whether a tumor responds to a drug will be by evaluating the tumor itself, within its own microenvironment. To this end, Jonas et al. created miniature drug delivery vessels that can be implanted with a standard biopsy needle directly into the tumor. These vessels, less than 1 mm in diameter, contained up to 16 microwells that each released a bolus of drug into the surrounding tumor tissue. The device and its surrounding tissue were then removed with a larger coring needle to see if the cancer cells had responded to the drug—or combination of drugs. In mouse models of melanoma, breast, or prostate cancers, the local response to a common chemotherapeutic, doxorubicin, matched the tumor response to systemic therapy. Furthermore, in a mouse model of triple-negative breast cancer, tumor sensitivity to five different locally delivered cancer drugs was identical to tumor response after intravenous administration of drug; for instance, tumors were most responsive to paclitaxel and least responsive to lapatinib. Such tiny drug-releasing devices can be implanted at different locations within the tumor, overcoming issues with tumor heterogeneity, and allowing for reproducible evaluation of drug sensitivity directly within the patient. Current anticancer chemotherapy relies on a limited set of in vitro or indirect prognostic markers of tumor response to available drugs. A more accurate analysis of drug sensitivity would involve studying tumor response in vivo. To this end, we have developed an implantable device that can perform drug sensitivity testing of several anticancer agents simultaneously inside the living tumor. The device contained reservoirs that released microdoses of single agents or drug combinations into spatially distinct regions of the tumor. The local drug concentrations were chosen to be representative of concentrations achieved during systemic treatment. Local efficacy and drug concentration profiles were evaluated for each drug or drug combination on the device, and the local efficacy was confirmed to be a predictor of systemic efficacy in vivo for multiple drugs and tumor models. Currently, up to 16 individual drugs or combinations can be assessed independently, without systemic drug exposure, through minimally invasive biopsy of a small region of a single tumor. This assay takes into consideration physiologic effects that contribute to drug response by allowing drugs to interact with the living tumor in its native microenvironment. Because these effects are crucial to predicting drug response, we envision that these devices will help identify optimal drug therapy before systemic treatment is initiated and could improve drug response prediction beyond the biomarkers and in vitro and ex vivo studies used today. These devices may also be used in clinical drug development to safely gather efficacy data on new compounds before pharmacological optimization.