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Desmoplastic pancreatic tumors exhibit excessive extracellular matrix (ECM) and are thus highly resistant to anticancer therapeutics, since the ECM restricts drug penetration and dispersion. Here, we designed and generated two hypoxia\u2010responsive and cancer\u2010specific hybrid promoters, H(mT)E and H(E)mT. Transgene expression driven by each hybrid promoter was markedly higher under hypoxic conditions than normoxic conditions. Moreover, H(E)mT\u2010driven transgene expression was highly cancer\u2010specific and was superior to that of H(mT)E\u2010driven expression. A decorin\u2010expressing oncolytic adenovirus (Ad; oH(E)mT\u2010DCN) replicating under the control of the H(E)mT promoter induced more potent and highly cancer\u2010specific cell death compared with its cognate control oncolytic Ad, which harbored the endogenous Ad E1A promoter. Moreover, oH(E)mT\u2010DCN exhibited enhanced antitumor efficacy compared with both the clinically approved oncolytic Ad ONYX\u2010015 and its cognate control oncolytic Ad lacking DCN. oH(E)mT\u2010DCN treatment also attenuated the expression of major ECM components, such as collagen I\/III, elastin and fibronectin and induced tumor cell apoptosis, leading to extensive viral dispersion within orthotopic pancreatic tumors and pancreatic cancer patient\u2010derived tumor spheroids. Collectively, these findings demonstrate that oH(E)mT\u2010DCN exhibits potent antitumor efficacy by degrading the ECM and inducing apoptosis in a multifunctional process. This process facilitates the dispersion and replication of oncolytic Ad, making it an attractive candidate for the treatment of aggressive and desmoplastic pancreatic cancer.<\/jats:p>","DOI":"10.1002\/ijc.31060","type":"journal-article","created":{"date-parts":[[2017,9,20]],"date-time":"2017-09-20T08:18:52Z","timestamp":1505895532000},"page":"392-413","source":"Crossref","is-referenced-by-count":28,"title":["Potent antitumor effect of tumor microenvironment\u2010targeted oncolytic adenovirus against desmoplastic pancreatic cancer"],"prefix":"10.1002","volume":"142","author":[{"given":"Yan","family":"Li","sequence":"first","affiliation":[{"name":"Graduate Program for Nanomedical Science, Yonsei University Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JinWoo","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Bioengineering College of Engineering, Hanyang University, Seongdong\u2010Gu Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joung\u2010Eun","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Bioengineering College of Engineering, Hanyang University, Seongdong\u2010Gu Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A\u2010Rum","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Bioengineering College of Engineering, Hanyang University, Seongdong\u2010Gu Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9466-4531","authenticated-orcid":false,"given":"Chae\u2010Ok","family":"Yun","sequence":"additional","affiliation":[{"name":"Department of Bioengineering College of Engineering, Hanyang University, Seongdong\u2010Gu Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,10,9]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdu138"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21166"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-62703-287-2_9"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/cgt.2011.7"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1159\/000150339"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1517\/14712590903559822"},{"key":"e_1_2_6_8_1","first-page":"1666","article-title":"Phase III randomized clinical trial of intratumoral injection of E1B gene\u2010deleted adenovirus (H101) combined with cisplatin\u2010based chemotherapy in treating squamous cell cancer of head and neck or esophagus","volume":"23","author":"Xia ZJ","year":"2004","journal-title":"Ai Zheng"},{"key":"e_1_2_6_9_1","article-title":"RHIA. 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