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INSULIN‐LIKE GROWTH FACTOR‐I RECEPTOR AS A CANDIDATE FOR A NOVEL MOLECULAR TARGET IN GASTROINTESTINAL CANCERS
Author(s) -
Adachi Yasushi,
Yamamoto Hiroyuki,
Imsumran Arisa,
Oka Toshikuni,
Oki Mariko,
Nosho Katsuhiko,
Min Yongfen,
Shinomura Yasuhisa,
Lee ChoonTaek,
Carbone David P.,
Imai Kohzoh
Publication year - 2006
Publication title -
digestive endoscopy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.5
H-Index - 56
eISSN - 1443-1661
pISSN - 0915-5635
DOI - 10.1111/j.1443-1661.2006.00657.x
Subject(s) - insulin like growth factor receptor , cancer research , medicine , cancer , growth factor receptor inhibitor , growth factor , receptor , epidermal growth factor receptor , epidermal growth factor , downregulation and upregulation , insulin like growth factor , growth factor receptor , gastrointestinal cancer , biology , colorectal cancer , biochemistry , gene
Abnormal activation of growth factor receptors and their signal pathways are required for neoplastic transformation and tumor progression. The concept of targeting specific tumorigenic receptors has been validated by successful clinical application of multiple new drugs, such as those acting against HER2/neu, epidermal growth factor receptor 1, and c‐Kit. In this review, we focus on the next promising therapeutic molecular target of insulin‐like growth factor (IGF)‐I receptor (IGF‐Ir). The IGF/IGF‐Ir system is an important modifier of cancer cell proliferation, survival, growth, and treatment sensitivity in a number of neoplastic diseases, including human gastrointestinal carcinomas. Preclinical studies demonstrated that downregulation of IGF‐Ir signals reversed the neoplastic phenotype and sensitized cells to antitumor treatments. We summarize a variety of ways to disrupt IGF‐Ir function. Then, we introduce our strategy of adenoviruses expressing dominant negative of IGF‐Ir (IGF‐Ir/dn) against gastrointestinal cancers, including stomach, colon, and pancreas. IGF‐Ir/dn suppresses tumorigenicity both in vitro and in vivo and increases stressor‐induced apoptosis. IGF‐Ir/dn expression upregulates chemotherapy‐induced apoptosis and these combination therapies with chemotherapy are very effective against tumors in mice. Some drugs blocking IGF‐Ir function are now entering clinical trial, thus IGF‐Ir might be a candidate for a therapeutic target in several gastrointestinal malignancies.