000223248 001__ 223248
000223248 005__ 20180317092011.0
000223248 0247_ $$2doi$$a10.1158/1535-7163.Mct-15-0974
000223248 022__ $$a1535-7163
000223248 02470 $$2ISI$$a000385636300007
000223248 037__ $$aARTICLE
000223248 245__ $$aDebio 0617B Inhibits Growth of STAT3-Driven Solid Tumors through Combined Inhibition of JAK, SRC, and Class III/V Receptor Tyrosine Kinases
000223248 260__ $$aPhiladelphia$$bAmer Assoc Cancer Research$$c2016
000223248 269__ $$a2016
000223248 300__ $$a10
000223248 336__ $$aJournal Articles
000223248 520__ $$aTumor survival, metastases, chemoresistance, and escape from immune responses have been associated with inappropriate activation of STAT3 and/or STAT5 in various cancers, including solid tumors. Debio 0617B has been developed as a first-in-class kinase inhibitor with a unique profile targeting phospho-STAT3 (pSTAT3) and/or pSTAT5 in tumors through combined inhibition of JAK, SRC, ABL, and class III/V receptor tyrosine kinases (RTK). Debio 0617B showed dose-dependent inhibition of pSTAT3 in STAT3-activated carcinoma cell lines; Debio 0617B also showed potent antiproliferative activity in a panel of cancer cell lines and in patient-derived tumor xenografts tested in an in vitro clonogenic assay. Debio 0617B showed in vivo efficacy by inhibiting tumor growth in several mouse xenograft models. To increase in vivo efficacy and STAT3 inhibition, Debio 0617B was tested in combination with the EGFR inhibitor erlotinib in a non-small cell lung cancer xenograft model. To evaluate the impact of in vivo STAT3 blockade on metastases, Debio 0617B was tested in an orthotopic tumor model. Measurement of primary tumor weight and metastatic counts in lung tissue demonstrated therapeutic efficacy of Debio 0617B in this model. These data show potent activity of Debio 0617B on a broad spectrum of STAT3-driven solid tumors and synergistic activity in combination with EGFR inhibition. (C) 2016 AACR.
000223248 700__ $$aMurone, Maximilien$$uDebiopharm Int SA, Lausanne, Switzerland
000223248 700__ $$aChessex, Anne Vaslin$$uDebiopharm Int SA, Lausanne, Switzerland
000223248 700__ $$aAttinger, Antoine$$uDebiopharm Int SA, Lausanne, Switzerland
000223248 700__ $$aRamachandra, Raghuveer$$uAurigene Discovery Technol, Bangalore, Karnataka, India
000223248 700__ $$aShetty, Shankar J.$$uAurigene Discovery Technol, Bangalore, Karnataka, India
000223248 700__ $$aDaginakatte, Girish$$uAurigene Discovery Technol, Bangalore, Karnataka, India
000223248 700__ $$aSengupta, Saumitra$$uAurigene Discovery Technol, Bangalore, Karnataka, India
000223248 700__ $$aMarappan, Sivapriya$$uAurigene Discovery Technol, Bangalore, Karnataka, India
000223248 700__ $$aDhodheri, Samiulla$$uAurigene Discovery Technol, Bangalore, Karnataka, India
000223248 700__ $$aRigotti, Stefania$$uDebiopharm Int SA, Lausanne, Switzerland
000223248 700__ $$aBachhav, Yogeshwar$$uDebiopharm Int SA, Lausanne, Switzerland
000223248 700__ $$aBrienza, Silvano$$uDebiopharm Int SA, Lausanne, Switzerland
000223248 700__ $$aTraxler, Peter$$uDebiopharm Int SA, Lausanne, Switzerland
000223248 700__ $$aLang, Marc$$uDebiopharm Int SA, Lausanne, Switzerland
000223248 700__ $$0240585$$aAguet, Michel$$g168669$$uSwiss Fed Inst Technol, Lausanne, Switzerland
000223248 700__ $$aZoete, Vincent$$uSwiss Inst Bioinformat, Lausanne, Switzerland
000223248 700__ $$aMichielin, Olivier$$uSwiss Inst Bioinformat, Lausanne, Switzerland
000223248 700__ $$aNicholas, Courtney$$uUniv Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA
000223248 700__ $$aJohnson, Faye M.
000223248 700__ $$aRamachandra, Murali$$uAurigene Discovery Technol, Bangalore, Karnataka, India
000223248 700__ $$aMcallister, Andres
000223248 773__ $$j15$$k10$$q2334-2343$$tMolecular Cancer Therapeutics
000223248 909CO $$ooai:infoscience.tind.io:223248$$particle$$pSV
000223248 909C0 $$0252150$$pUPAGU$$xU11156
000223248 917Z8 $$x168669
000223248 937__ $$aEPFL-ARTICLE-223248
000223248 973__ $$aOTHER$$rREVIEWED$$sPUBLISHED
000223248 980__ $$aARTICLE