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Whereas sarcoma cells synthesize minimal ASMase, they take up gemcitabine poorly in vitro and in murine xenografts. A strategy designed to augment gemcitabine-induced ASMase secretion into the extravascular space by ASMase-rich neo-angiogenic cells, which then targets tumor cell plasma membranes, yields \u201cbystander\u201d CRPs on sarcoma cells and ENT1 insertion therein, conferring markedly enhanced gemcitabine uptake and xenograft response. Engaging this biology in a prospective phase II clinical trial in advanced sarcoma yielded robust volumetric changes in evaluated tumors that developed early and were often durable.<\/jats:p>","DOI":"10.1172\/jci183474","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T19:00:16Z","timestamp":1788462016000},"source":"Crossref","is-referenced-by-count":0,"title":["Enhancing gemcitabine uptake by promoting dimerization of ENT1 transporter improves response rates of patients with sarcoma"],"prefix":"10.1172","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1258-0105","authenticated-orcid":true,"given":"Aditya","family":"Ganju","sequence":"first","affiliation":[{"name":"Laboratory of Signal Transduction,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyam","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark 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