targeted morphoproteomic profiling of ewings sarcoma treated with insulin-like growth factor 1 receptor (igf1r) inhibitors responseresistance signatures目标morphoproteomic剖析尤文氏肉瘤的治疗胰岛素样生长因子1受体(igf1r)抑制剂responseresistance签名.pdf

Targeted Morphoproteomic Profiling of Ewing’s Sarcoma Treated with Insulin-Like Growth Factor 1 Receptor (IGF1R) Inhibitors: Response/Resistance Signatures 1,2 2 3 4 4 5 Vivek Subbiah *, Aung Naing , Robert E. Brown , Helen Chen , Laurence Doyle , Patricia LoRusso , 6 1 2 Robert Benjamin , Pete Anderson , Razelle Kurzrock 1 Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas, 2 Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas, 3 Department of Pathology and Laboratory Medicine, UT Health, University of Texas–Houston Medical School, Houston, Texas, 4 Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, Maryland, 5 Wayne State University–Barbara Ann Karmanos Cancer Institute, Detroit, Michigan, 6 Division of Cancer Medicine, Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas Abstract Background: Insulin-like growth factor 1 receptor (IGF1R) targeted therapies have resulted in responses in a small number of patients with advanced metastatic Ewing’s sarcoma. We performed morphoproteomic profiling to better understand response/resistance mechanisms of Ewing’s sarcoma to IGF1R inhibitor-based therapy. Methodology/Principal Findings: This pilot study assessed two patients with advanced Ewing’s sarcoma treated with IGF1R antibody alone followed by combined IGF1R inhibitor plus mammalian target of rapamycin (mTOR) inhibitor treatment once resistance to single-agent IGF1R inhibitor developed. Immunohistochemical probes were applie