PMID- 25617986 OWN - NLM STAT- MEDLINE DCOM- 20151116 LR - 20181202 IS - 1872-8332 (Electronic) IS - 0169-5002 (Linking) VI - 87 IP - 3 DP - 2015 Mar TI - Expression of insulin-like growth factor 1 receptor (IGF-1R) predicts poor responses to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in non-small cell lung cancer patients harboring activating EGFR mutations. PG - 311-7 LID - S0169-5002(15)00014-8 [pii] LID - 10.1016/j.lungcan.2015.01.004 [doi] AB - OBJECTIVES: Expression of insulin-like growth factor 1 receptor (IGF-1R) in non-small cell lung cancer (NSCLC) is associated with poor prognosis. The IGF-1R pathway activates downstream targets that bypass dependency in signals from the epidermal growth factor receptor (EGFR), which mediates resistance to EGFR tyrosine kinase inhibitors (TKIs). The aim of the present study was to determine the predictive role of IGF-1R expression in the response to EGFR-TKIs of NSCLC patients harboring activating EGFR mutations. MATERIALS AND METHODS: We retrospectively studied 62 NSCLC patients who had activating EGFR mutations and received TKIs. Protein expression of IGF-1R, vascular endothelial growth factor (VEGF), and human epidermal growth factor receptor 2 (HER2) were measured by immunohistochemical staining. Univariate and multivariate analyses were performed to identify predictive factors associated with the responses to EGFR-TKIs. The relationship of progression-free survival (PFS) with IGF-1R expression and the presence of diabetes mellitus (DM) were examined. RESULTS: Of 62 EGFR mutation positive patients, 26 expressed IGF-1R, and 13 had DM. In the multivariate analysis, young age, squamous cell carcinoma, and IGF-1R expression were independently associated with a shorter PFS after treatment with EGFR-TKIs. Patients expressing IGF-1R showed a significantly shorter PFS in response to EGFR-TKIs compared with those lacking IGF-1R expression (9.1 vs. 20.1 months, p=0.005). The 13 patients with DM were more likely to express IGF-1R (p=0.001) and had shorter PFS times when treated with first-line EGFR-TKIs (7.6 vs. 18.6 months, p=0.005), compared with those without DM. CONCLUSION: IGF-1R expression was a negative predictive factor for a response to EGFR-TKIs in NSCLC patients harboring activating EGFR mutations. Moreover, patients with DM highly expressed IGF-1R in tumor tissues, which was associated with a poor response to first-line TKI therapy. Further studies aimed at overcoming EGFR-TKI resistance will need to also address IGF-1R pathways. CI - Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved. FAU - Yeo, Chang Dong AU - Yeo CD AD - Division of Pulmonology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. FAU - Park, Ki Hoon AU - Park KH AD - Division of Pulmonology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. FAU - Park, Chan Kwon AU - Park CK AD - Division of Pulmonology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. FAU - Lee, Sang Haak AU - Lee SH AD - Division of Pulmonology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. FAU - Kim, Seung Joon AU - Kim SJ AD - Division of Pulmonology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. FAU - Yoon, Hyung Kyu AU - Yoon HK AD - Division of Pulmonology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. FAU - Lee, Youn Soo AU - Lee YS AD - Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. FAU - Lee, Eun Jung AU - Lee EJ AD - Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. FAU - Lee, Kyo Young AU - Lee KY AD - Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. FAU - Kim, Tae-Jung AU - Kim TJ AD - Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address: kimecho@catholic.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150114 PL - Ireland TA - Lung Cancer JT - Lung cancer (Amsterdam, Netherlands) JID - 8800805 RN - 0 (Antineoplastic Agents) RN - 0 (Protein Kinase Inhibitors) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 2.7.10.1 (Receptor, IGF Type 1) SB - IM MH - Adult MH - Aged MH - Antineoplastic Agents/therapeutic use MH - Carcinoma, Non-Small-Cell Lung/drug therapy/*genetics/*mortality/pathology MH - Comorbidity MH - ErbB Receptors/antagonists & inhibitors/*genetics MH - Female MH - *Gene Expression MH - Humans MH - Lung Neoplasms/drug therapy/*genetics/*mortality/pathology MH - Male MH - Middle Aged MH - *Mutation MH - Neoplasm Metastasis MH - Neoplasm Staging MH - Patient Outcome Assessment MH - Prognosis MH - Protein Kinase Inhibitors/therapeutic use MH - Receptor, IGF Type 1/*genetics MH - Risk Factors MH - Survival Analysis OTO - NOTNLM OT - DM OT - EGFR mutation OT - IGF-1R OT - Non-small cell lung cancer OT - Progression-free survival OT - TKI EDAT- 2015/01/27 06:00 MHDA- 2015/11/17 06:00 CRDT- 2015/01/26 06:00 PHST- 2014/11/28 00:00 [received] PHST- 2014/12/29 00:00 [revised] PHST- 2015/01/03 00:00 [accepted] PHST- 2015/01/26 06:00 [entrez] PHST- 2015/01/27 06:00 [pubmed] PHST- 2015/11/17 06:00 [medline] AID - S0169-5002(15)00014-8 [pii] AID - 10.1016/j.lungcan.2015.01.004 [doi] PST - ppublish SO - Lung Cancer. 2015 Mar;87(3):311-7. doi: 10.1016/j.lungcan.2015.01.004. Epub 2015 Jan 14.