Saha, BiswajitMathur, TanmayTronolone, James J.Chokshi, MithilLokhande, Giriraj K.Selahi, AmiraliGaharwar, Akhilesh K.Afshar-Kharghan, VahidSood, Anil K.Bao, GangJain, Abhishek2021-08-052021-08-052021Saha, Biswajit, Mathur, Tanmay, Tronolone, James J., et al.. "Human tumor microenvironment chip evaluates the consequences of platelet extravasation and combinatorial antitumor-antiplatelet therapy in ovarian cancer." <i>Science Advances,</i> 7, no. 30 (2021) AAAS: https://doi.org/10.1126/sciadv.abg5283.https://hdl.handle.net/1911/111136Platelets extravasate from the circulation into tumor microenvironment, enable metastasis, and confer resistance to chemotherapy in several cancers. Therefore, arresting tumor-platelet cross-talk with effective and atoxic antiplatelet agents in combination with anticancer drugs may serve as an effective cancer treatment strategy. To test this concept, we create an ovarian tumor microenvironment chip (OTME-Chip) that consists of a platelet-perfused tumor microenvironment and which recapitulates platelet extravasation and its consequences. By including gene-edited tumors and RNA sequencing, this organ-on-chip revealed that platelets and tumors interact through glycoprotein VI (GPVI) and tumor galectin-3 under shear. Last, as proof of principle of a clinical trial, we showed that a GPVI inhibitor, Revacept, impairs metastatic potential and improves chemotherapy. Since GPVI is an antithrombotic target that does not impair hemostasis, it represents a safe cancer therapeutic. We propose that OTME-Chip could be deployed to study other vascular and hematological targets in cancer. A tumor microenvironment chip reveals how platelets may fuel cancer metastasis and chemoresistance and unravels a new treatment. A tumor microenvironment chip reveals how platelets may fuel cancer metastasis and chemoresistance and unravels a new treatment.engThis is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Journal articleeabg5283-fullhttps://doi.org/10.1126/sciadv.abg5283