{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T22:18:53Z","timestamp":1777501133994,"version":"3.51.4"},"reference-count":44,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,11,1]],"date-time":"2019-11-01T00:00:00Z","timestamp":1572566400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2020,1,15]]},"abstract":"<jats:p>Bladder cancer is the sixth most common cancer in the United States, and it exhibits an alarming 70% recurrence rate. Thus, the development of more efficient antibladder cancer approaches is a high priority. Accordingly, this work provides the basis for a transformative anticancer strategy that takes advantage of the unique characteristics of the bladder. Unlike mucin\u2010shielded normal bladder cells, cancer cells are exposed to the bladder lumen and overexpress EGFR. Therefore, we used an EGF\u2010conjugated anthrax toxin that after targeting EGFR was internalized and triggered apoptosis in exposed bladder cancer cells. This unique agent presented advantages over other EGF\u2010based technologies and other toxin\u2010derivatives. In contrast to known agents, this EGF\u2010toxin conjugate promoted its own uptake <jats:italic>via<\/jats:italic> receptor microclustering even in the presence of Her2 and induced cell death with a LC<jats:sub>50<\/jats:sub> &lt;\u20091 nM. Furthermore, our data showed that exposures as short as \u22483 min were enough to commit human (T24), mouse (MB49) and canine (primary) bladder cancer cells to apoptosis. Exposure of tumor\u2010free mice and dogs with the agent resulted in no toxicity. In addition, the EGF\u2010toxin was able to eliminate cells from human patient tumor samples. Importantly, the administration of EGF\u2010toxin to dogs with spontaneous bladder cancer, who had failed or were not eligible for other therapies, resulted in ~30% average tumor reduction after one treatment cycle. Because of its <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> high efficiency, fast action (reducing treatment time from hours to minutes) and safety, we propose that this EGF\u2013anthrax toxin conjugate provides the basis for new, transformative approaches against bladder cancer.<\/jats:p>","DOI":"10.1002\/ijc.32719","type":"journal-article","created":{"date-parts":[[2019,10,4]],"date-time":"2019-10-04T12:23:11Z","timestamp":1570191791000},"page":"449-460","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["A novel, safe, fast and efficient treatment for Her2\u2010positive and negative bladder cancer utilizing an EGF\u2010anthrax toxin chimera"],"prefix":"10.1002","volume":"146","author":[{"given":"Sherwin","family":"Jack","sequence":"first","affiliation":[{"name":"Purdue University Center for Cancer Research  West Lafayette IN"},{"name":"Department of Biological Sciences Purdue University  West Lafayette IN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kayalvizhi","family":"Madhivanan","sequence":"additional","affiliation":[{"name":"Purdue University Center for Cancer Research  West Lafayette IN"},{"name":"Department of Biological Sciences Purdue University  West Lafayette IN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Swetha","family":"Ramadesikan","sequence":"additional","affiliation":[{"name":"Purdue University Center for Cancer Research  West Lafayette IN"},{"name":"Department of Biological Sciences Purdue University  West Lafayette IN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sneha","family":"Subramanian","sequence":"additional","affiliation":[{"name":"Purdue University Center for Cancer Research  West Lafayette IN"},{"name":"Department of Biological Sciences Purdue University  West Lafayette IN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"II","given":"Daniel F.","family":"Edwards","sequence":"additional","affiliation":[{"name":"Purdue University Center for Cancer Research  West Lafayette IN"},{"name":"Department of Biological Sciences Purdue University  West Lafayette IN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bennett D.","family":"Elzey","sequence":"additional","affiliation":[{"name":"Purdue University Center for Cancer Research  West Lafayette IN"},{"name":"Department of Comparative Pathobiology Purdue University  West Lafayette IN"},{"name":"Department of Urology Indiana University School of Medicine  Indianapolis IN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deepika","family":"Dhawan","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Sciences Purdue University  West Lafayette IN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"McCluskey","sequence":"additional","affiliation":[{"name":"Department of Microbiology Harvard Medical School  Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin M.","family":"Kischuk","sequence":"additional","affiliation":[{"name":"Purdue University Center for Cancer Research  West Lafayette IN"},{"name":"Department of Comparative Pathobiology Purdue University  West Lafayette IN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander R.","family":"Loftis","sequence":"additional","affiliation":[{"name":"Department of Chemistry Massachusetts Institute of Technology  Cambridge MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas","family":"Truex","sequence":"additional","affiliation":[{"name":"Department of Chemistry Massachusetts Institute of Technology  Cambridge MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Chemistry Massachusetts Institute of Technology  Cambridge MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mike","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Chemistry Massachusetts Institute of Technology  Cambridge MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy","family":"Rabideau","sequence":"additional","affiliation":[{"name":"Department of Chemistry Massachusetts Institute of Technology  Cambridge MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bradley","family":"Pentelute","sequence":"additional","affiliation":[{"name":"Department of Chemistry Massachusetts Institute of Technology  Cambridge MA"},{"name":"Koch Institute MIT  Cambridge MA"},{"name":"Broad Institute of Harvard and MIT  Cambridge MA"},{"name":"Center for Environmental Health Sciences MIT  Cambridge MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Collier","sequence":"additional","affiliation":[{"name":"Department of Microbiology Harvard Medical School  Boston MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hristos","family":"Kaimakliotis","sequence":"additional","affiliation":[{"name":"Department of Urology Indiana University School of Medicine  Indianapolis IN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Koch","sequence":"additional","affiliation":[{"name":"Department of Urology Indiana University School of Medicine  Indianapolis IN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy L.","family":"Ratliff","sequence":"additional","affiliation":[{"name":"Purdue University Center for Cancer Research  West Lafayette IN"},{"name":"Department of Comparative Pathobiology Purdue University  West Lafayette IN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah W.","family":"Knapp","sequence":"additional","affiliation":[{"name":"Purdue University Center for Cancer Research  West Lafayette IN"},{"name":"Department of Veterinary Clinical Sciences Purdue University  West Lafayette IN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5623-0073","authenticated-orcid":false,"given":"Ruben C.","family":"Aguilar","sequence":"additional","affiliation":[{"name":"Purdue University Center for Cancer Research  West Lafayette IN"},{"name":"Department of Biological Sciences Purdue University  West Lafayette IN"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,11]]},"reference":[{"key":"e_1_2_8_2_1","volume-title":"Cancer facts and figures 2018","author":"Society AC","year":"2018"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2016.12.090"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOU.0000000000000078"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00345-009-0395-z"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3233\/BLC-150042"},{"key":"e_1_2_8_7_1","volume-title":"Treatment of bladder cancer by stage","author":"ACS","year":"2019"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1442-2042.2010.02584.x"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1590\/S1677-55382009000600002"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.5489\/cuaj.1196"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2007.09.003"},{"key":"e_1_2_8_12_1","first-page":"323","article-title":"Bladder cancer: current optimal intravesical treatment","volume":"25","author":"Lamm DL","year":"2005","journal-title":"Urol Nurs"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(06)00264-3"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euf.2018.06.018"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.3233\/BLC-179018"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-004-1005-4"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2011.07.017"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2009.10.006"},{"key":"e_1_2_8_19_1","first-page":"563","article-title":"Increased bladder permeability in interstitial cystitis\/painful bladder syndrome","volume":"4","author":"Hurst RE","year":"2015","journal-title":"Transl Androl Urol"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.3233\/BLC-160056"},{"key":"e_1_2_8_21_1","first-page":"2530","article-title":"Clinical implications of the expression of epidermal growth factor receptors in human transitional cell carcinoma","volume":"50","author":"Messing EM","year":"1990","journal-title":"Cancer Res"},{"key":"e_1_2_8_22_1","first-page":"1130","article-title":"Coregulation of epidermal growth factor receptor\/human epidermal growth factor receptor 2 (HER2) levels and locations: quantitative analysis of HER2 overexpression effects","volume":"63","author":"Hendriks BS","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18112420"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.160374"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.26413"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200210028"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxins3030294"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-1258"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.75.103004.142728"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxins9080236"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00088-12"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molonc.2012.12.003"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/ilar\/ilu018"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tvjl.2017.12.008"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxins4080580"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-6611"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdn749"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.28767"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0601469103"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/17.suppl_5.66"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1053\/prrv.2000.0102"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.12.6.1897"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2013.11.002"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0502159102"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0136688"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.32719","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ijc.32719","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.32719","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T09:50:19Z","timestamp":1694253019000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.32719"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11]]},"references-count":44,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,1,15]]}},"alternative-id":["10.1002\/ijc.32719"],"URL":"https:\/\/doi.org\/10.1002\/ijc.32719","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11]]},"assertion":[{"value":"2019-05-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-09-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-11-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}