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To identify the targetable inhibitors of the ERK\/MAPK pathway, we performed a repurposing screening of a panel of antimicrobial agents in gastric cancer cells using an ERK\/MAPK\u2010driven firefly luciferase reporter assay. Multiple antibiotics were identified to inhibit ERK\u2010mediated transcriptional activity. Among them, doxycycline showed high inhibition of ERK\/MAPK\u2010regulated transcriptional activity and the levels of ERK proteins. Doxycycline was further identified to inhibit the proliferation and the colony\u2010 and spheroid\u2010forming potential of gastric cancer cells. By <jats:italic>in vitro<\/jats:italic> signaling pathway and genome\u2010wide expression profiling analyses, doxycycline was identified to inhibit signaling pathways and transcriptional activities regulated by ER, Myc, E2F1, Wnt, SMAD2\/3\/4, Notch, and OCT4. Doxycycline was also found to activate p53\u2010, ATF6\u2010, NRF1\/2\u2010, and MTF1\u2010mediated transcription and inhibit the transcription of histones, proteasomal genes, fibroblast growth factor, and other oncogenic factors. These observations show the multitargeting and targeted therapeutic features of doxycycline for a subset of gastric tumors.<\/jats:p>","DOI":"10.1111\/nyas.14288","type":"journal-article","created":{"date-parts":[[2020,1,16]],"date-time":"2020-01-16T06:14:45Z","timestamp":1579155285000},"page":"94-111","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Identification of the targeted therapeutic potential of doxycycline for a subset of gastric cancer patients"],"prefix":"10.1111","volume":"1467","author":[{"given":"Jaishree","family":"Pandian","sequence":"first","affiliation":[{"name":"Unit of Excellence in Cancer Genetics, Department of Genetics, Centre for Excellence in Genomic Sciences, School of Biological Sciences Madurai Kamaraj University  Madurai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ponmathi","family":"Panneerpandian","sequence":"additional","affiliation":[{"name":"Unit of 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