Abstract
Insulin-like growth factors (IGFs) play important roles in mammalian growth, development, aging, and diseases. Aberrant IGFs signaling may lead to malignant transformation and tumor progression, thus providing the rationale for targeting IGF axis in cancer. However, clinical trials of the type I IGF receptor (IGF-IR)-targeted agents have been largely disappointing. Accumulating evidence demonstrates that the IGF axis not only promotes tumorigenesis, but also confers resistance to standard treatments. Furthermore, there are diverse pathways leading to the resistance to IGF-IR-targeted therapy. Recent studies characterizing the complex IGFs signaling in cancer have raised hope to refine the strategies for targeting the IGF axis. This review highlights the biological activities of IGF-IR signaling in cancer and the contribution of IGF-IR to cytotoxic, endocrine, and molecular targeted therapies resistance. Moreover, we update the diverse mechanisms underlying resistance to IGF-IR-targeted agents and discuss the strategies for future development of the IGF axis-targeted agents.
Keywords:
Cancer; Drug resistance; Insulin-like growth factor; Receptor tyrosine kinase; Tumorigenesis.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use*
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Antineoplastic Agents, Hormonal / pharmacology
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Antineoplastic Agents, Hormonal / therapeutic use
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Cell Nucleus / metabolism
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Cell Physiological Phenomena / drug effects
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Cell Physiological Phenomena / physiology
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Cell Self Renewal / physiology
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Cell Transformation, Neoplastic*
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Clinical Trials as Topic
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Combined Modality Therapy
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DNA Damage
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DNA, Neoplasm / drug effects
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DNA, Neoplasm / radiation effects
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Disease Progression
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Drug Development
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Drug Resistance, Neoplasm / physiology*
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Epithelial-Mesenchymal Transition / physiology
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Gene Expression Regulation, Neoplastic / physiology
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Humans
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Integrins / physiology
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Molecular Targeted Therapy*
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Neoplasm Metastasis
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Neoplasm Proteins / antagonists & inhibitors
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Neoplasm Proteins / physiology*
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Neoplasms / drug therapy*
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Neoplasms / physiopathology
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Neoplasms / radiotherapy
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Protein Kinase Inhibitors / pharmacology
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Protein Kinase Inhibitors / therapeutic use*
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Receptor, IGF Type 1 / antagonists & inhibitors
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Receptor, IGF Type 1 / physiology*
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Signal Transduction / physiology*
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Somatomedins / physiology*
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Tumor Microenvironment
Substances
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Antineoplastic Agents
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Antineoplastic Agents, Hormonal
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DNA, Neoplasm
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IGF1R protein, human
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Integrins
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Neoplasm Proteins
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Protein Kinase Inhibitors
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Somatomedins
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Receptor, IGF Type 1