{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:09:24Z","timestamp":1779235764634,"version":"3.51.4"},"reference-count":18,"publisher":"American Society for Clinical Investigation","issue":"6","license":[{"start":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T00:00:00Z","timestamp":1710460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,15]]},"abstract":"<jats:p>\n                    Diffuse intrinsic pontine glioma (DIPG) is a devastating brain tumor with a need for novel therapies. So far, monotherapies have failed to prolong survival for these patients, and combinatorial strategies have often shown severe, dose-limiting toxicities. In this issue of the\n                    <jats:italic>JCI<\/jats:italic>\n                    , Duchatel, Jackson, and colleagues address this challenge by introducing a drug combination that mitigates side effects and overcomes resistance. After identifying the PI3K\/mTOR pathway as a therapeutic vulnerability, they treated DIPG-bearing mice with paxalisib and saw responses but also observed hyperglycemia as a severe side effect. Combining paxalisib with metformin mitigated this toxicity, but also upregulated protein kinase C (PKC) signaling. To tackle this mechanism of resistance, the authors added the PKC inhibitor enzastaurin to their drug combination and showed that this triple therapy led to improved survival. This approach paves the way for improved outcomes for patients with DIPG and other brain tumors.\n                  <\/jats:p>","DOI":"10.1172\/jci179144","type":"journal-article","created":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T14:00:34Z","timestamp":1710424834000},"source":"Crossref","is-referenced-by-count":5,"title":["Just a spoonful of metformin helps the medicine go down"],"prefix":"10.1172","volume":"134","author":[{"given":"Theophilos","family":"Tzaridis","sequence":"first","affiliation":[{"name":"Cancer Genome and Epigenetics Program, NCI-Designated Cancer Center, Sanford Burnham, Prebys Medical Discovery Institute, La Jolla, California, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert J.","family":"Wechsler-Reya","sequence":"additional","affiliation":[{"name":"Cancer Genome and Epigenetics Program, NCI-Designated Cancer Center, Sanford Burnham, Prebys Medical Discovery Institute, La Jolla, California, USA."},{"name":"Department of Neurology and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"232","published-online":{"date-parts":[[2024,3,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.12622"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI170329"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-23-0131"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-019-03271-3"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-23-0186"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaw0064"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdu444"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noz071"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-2808"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1126\/science.aao4750"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-014-0082-4"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.32337"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.4103\/0976-0105.177703"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-023-04263-8"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noad117"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0343-4"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noad073.168"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1002\/onco.13674"}],"container-title":["Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jci.org\/articles\/view\/179144\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T23:34:54Z","timestamp":1779233694000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jci.org\/articles\/view\/179144"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,15]]},"references-count":18,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,1,16]]},"published-print":{"date-parts":[[2024,3,15]]}},"alternative-id":["10.1172\/JCI179144"],"URL":"https:\/\/doi.org\/10.1172\/jci179144","relation":{},"ISSN":["1558-8238"],"issn-type":[{"value":"1558-8238","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,15]]},"article-number":"e179144"}}