title: An implantable microdevice to perform high-throughput in vivo drug sensitivity testing in tumors.
abstract: 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.
authors.affiliation: The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Oliver
authors.initials: O
authors.lastname: Jonas
authors.affiliation: The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Landry
authors.affiliation: The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Kibur Medical Inc., 29 Newbury Street, Suite 301, Boston, MA 02116, USA.
authors.forename: Jason E
authors.initials: JE
authors.lastname: Fuller
authors.affiliation: Kibur Medical Inc., 29 Newbury Street, Suite 301, Boston, MA 02116, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Santini
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Jose
authors.initials: J
authors.lastname: Baselga
authors.affiliation: Kibur Medical Inc., 29 Newbury Street, Suite 301, Boston, MA 02116, USA. Third Rock Ventures LLC, 29 Newbury Street, Boston, MA 02116, USA.
authors.forename: Robert I
authors.initials: RI
authors.lastname: Tepper
authors.affiliation: The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Department of Materials Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Cima
authors.affiliation: The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. rlanger@mit.edu.
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D014408:Biomarkers, Tumor; D001706:Biopsy; D002138:Calibration; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000737:chemistry; D016503:Drug Delivery Systems; D016903:Drug Monitoring / Q000295:instrumentation*; D004354:Drug Screening Assays, Antitumor / Q000295:instrumentation* / Q000379:methods; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011379:Prognosis
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D011108:Polymers; D011092:Polyethylene Glycols; D004317:Doxorubicin