Targeting insulin-like growth factor 1 receptor in sarcomas

被引:93
作者
Scotlandi, Katia [1 ]
Picci, Piero [1 ]
机构
[1] Ist Ortoped Rizzoli, Lab Oncol Res, I-40136 Bologna, Italy
关键词
biomarkers; insulin-like growth factor-1 receptor; metabolism; sarcomas; targeted therapies;
D O I
10.1097/CCO.0b013e328302edab
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose of review The present review examines the rationale for targeting insulin-like growth factor-1 receptor in sarcoma therapy and highlights some key issues that need to be addressed as clinical trials targeting insulin-like growth factor-1 receptor proceed. Recent findings Preclinical evidence supports proof of principle for targeting insulin-like growth factor-1 receptor signaling in sarcomas. The insulin-like growth factor system is activated by or associated with most of the fusion oncoproteins that genetically characterize a group of sarcomas, but alterations in this pathway appear as a common feature. Correlation of cancer risk with insulin-like growth factor-1 receptor signaling expression and polymorphisms has also been described. Blockade of insulin-like growth factor-1 receptor functions results in an inhibition of tumor growth and metastasis, both when the targeted drugs were used as single agents and in combined therapies. Antibodies against insulin-like growth factor-1 receptor and small kinase inhibitors represent, at this point, the most probable clinical options. Summary Sarcomas are good candidates for the design of a clinical study targeting insulin-like growth factor-1 receptor. An attention to schedule with chemotherapy agents and new drugs, measurement of relevant indicators of response and better molecular understanding of the metabolic functions of insulin-like growth facto-1 receptor and its functional relationship with insulin receptor are necessary to proceed safely with the design of anti-insulin-like growth factor strategies.
引用
收藏
页码:419 / 427
页数:9
相关论文
共 80 条
[51]   Transcriptional activation of the insulin-like growth factor I receptor gene by the Kruppel-like factor 6 (KLF6) tumor suppressor protein: Potential interactions between KLF6 and p53 [J].
Rubinstein, M ;
Idelman, G ;
Plymate, SR ;
Narla, G ;
Friedman, SL ;
Werner, H .
ENDOCRINOLOGY, 2004, 145 (08) :3769-3777
[52]  
Sachdev D, 2003, CANCER RES, V63, P627
[53]   Disrupting insulin-like growth factor signaling as a potential cancer therapy [J].
Sachdev, Deepali ;
Yee, Douglas .
MOLECULAR CANCER THERAPEUTICS, 2007, 6 (01) :1-12
[54]   The role of the IGF system in cancer growth and metastasis: Overview and recent insights [J].
Samani, Amir Abbas ;
Yakar, Shoshana ;
LeRoith, Derek ;
Brodt, Pnina .
ENDOCRINE REVIEWS, 2007, 28 (01) :20-47
[55]   Transcriptional regulation of the insulin-like growth factor-1 receptor gene in breast cancer [J].
Sarfstein, Rive ;
Maor, Sharon ;
Reizner, Naama ;
Abramovitch, Shirley ;
Werner, Haim .
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2006, 252 (1-2) :241-246
[56]   Analysis of genes critical for growth regulation identifies insulin-like growth factor 2 receptor variations with possible functional significance as risk factors for osteosarcoma [J].
Savage, Sharon A. ;
Woodson, Karen ;
Walk, Elyse ;
Modi, William ;
Liao, Jason ;
Douglass, Chester ;
Hoover, Robert N. ;
Chanock, Stephen J. .
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2007, 16 (08) :1667-1674
[57]   Antitumor activity of the insulin-like growth factor-I receptor kinase inhibitor NVP-AEW541 in musculoskeletal tumors [J].
Scotlandi, K ;
Manara, MC ;
Nicoletti, G ;
Lollini, PL ;
Lukas, S ;
Benini, S ;
Croci, S ;
Perdichizzi, S ;
Zamberi, D ;
Serra, M ;
García-Echeverría, C ;
Hofmann, F ;
Picci, P .
CANCER RESEARCH, 2005, 65 (09) :3868-3876
[58]   Prognostic and therapeutic relevance of HER2 expression in osteosarcoma and Ewing's sarcoma [J].
Scotlandi, K ;
Manara, MC ;
Hattinger, CM ;
Benini, S ;
Perdichizzi, S ;
Pasello, M ;
Bacci, G ;
Zanella, L ;
Bertoni, F ;
Picci, P ;
Serra, M .
EUROPEAN JOURNAL OF CANCER, 2005, 41 (09) :1349-1361
[59]  
Scotlandi K, 1996, CANCER RES, V56, P4570
[60]  
Scotlandi K, 1998, CANCER RES, V58, P4127