FOCUS INTERGROUP COLLABORATION AGAINST SARCOMAS (ICAS) FOCUS Biologically targeted therapeuticsBiologically targeted therapeutics Histology specificHistology specific Facilitate Intergroup CollaborationFacilitate Intergroup Collaboration

Growth Factor Receptor Expression in Sarcomas Growth Factor Receptor Expression in Sarcomas Sarcoma EGF-R* PDGF-R** MPNST 7/7 † -- Synovial Cell* 17/25 0/2 Fibrosarcoma8/11 -- MFH 12/1711/12 Liposarcoma -- 9/12 Leiomyosarcoma-- 3/7 * Common (70%) SSX1 translocation: Her2 21/32 Her4 12/13 †JCI 105: * L Baker et al AACR 2002 **Can Res 50:

INTERGROUP SARCOMA COMMITTEE HER2 and Cox-2 Expression in Synovial Sarcomas Her2/neu Cox-2

EGF-R EXPRESSION AND INHIBITION IN MPNST Intense membrane staining EGF-R inhibitors DeClue et al JCI 2000 DeClue et al JCI 2000

ICAS STUDIES Metastatic Disease ICAS #SarcomaTarget Inhibitor Prior Rx S0330MPNSTEGF-R erlotinib N S0345DFSPPDGF-R imatinibY S0346SynovialHER2* trastuzumabY S0505STSVEGF sorafenibY

ICAS STUDIES Metastatic Disease ICAS #SarcomaTarget Inhibitor Prior Rx S0423 ChondroMTAP pemetrexedY S0502 GISTVEGF bevacizumabN S0416(COG) GIST(<30) kit imatinibN S0406(RTOG) STSCOX-2 celocoxibY EWS0031(COG) Ewing’s dose density chemoN

ICAS STUDIES Primary Disease ICAS #SarcomaTarget Inhibitor Prior Rx S0344 Chondro local surgery telomerase S0405(COG) Synovialbcl-2 anti-sense N S0404(ACSOG) STS array/microscopy N ACOSOG STSretroperitoneal XRT N

ICAS NEW ERA 2000   MOLECULAR REDEFINITION  IMPROVE PRIMARY MANAGEMENT  IDENTIFY TARGETED THERAPIES