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Small is beautiful: insulin-like growth factors and their role in growth, development, and cancer.

ABSTRACT: Insulin-like growth factors were discovered more than 50 years ago as mediators of growth hormone that effect growth and differentiation of bone and skeletal muscle. Interest of the role of insulin-like growth factors in cancer reached a peak in the 1990s, and then waned until the availability in the past 5 years of monoclonal antibodies and small molecules that block the insulin-like growth factor 1 receptor. In this article, we review the history of insulin-like growth factors and their role in growth, development, organism survival, and in cancer, both epithelial cancers and sarcomas. Recent developments regarding phase I to II clinical trials of such agents are discussed, as well as potential studies to consider in the future, given the lack of efficacy of one such monoclonal antibody in combination with cytotoxic chemotherapy in a first-line study in metastatic non-small-cell lung adenocarcinoma. Greater success with these agents clinically is expected when combining the agents with inhibitors of other cell signaling pathways in which cross-resistance has been observed.

SUBMITTER: Maki RG

PROVIDER: S-EPMC3039924 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Small is beautiful: insulin-like growth factors and their role in growth, development, and cancer.

Maki Robert G RG

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20101025 33

Insulin-like growth factors were discovered more than 50 years ago as mediators of growth hormone that effect growth and differentiation of bone and skeletal muscle. Interest of the role of insulin-like growth factors in cancer reached a peak in the 1990s, and then waned until the availability in the past 5 years of monoclonal antibodies and small molecules that block the insulin-like growth factor 1 receptor. In this article, we review the history of insulin-like growth factors and their role i ...[more]

PMID: 20975071

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Project description:Hormones are largely responsible for the integrated communication of several physiological systems responsible for modulating cellular growth and development. Although the specific hormonal influence must be considered within the context of the entire endocrine system and its relationship with other physiological systems, three key hormones are considered the "anabolic giants" in cellular growth and repair: testosterone, the growth hormone superfamily, and the insulin-like growth factor (IGF) superfamily. In addition to these anabolic hormones, glucocorticoids, mainly cortisol must also be considered because of their profound opposing influence on human skeletal muscle anabolism in many instances. This review presents emerging research on: (1) Testosterone signaling pathways, responses, and adaptations to resistance training; (2) Growth hormone: presents new complexity with exercise stress; (3) Current perspectives on IGF-I and physiological adaptations and complexity these hormones as related to training; and (4) Glucocorticoid roles in integrated communication for anabolic/catabolic signaling. Specifically, the review describes (1) Testosterone as the primary anabolic hormone, with an anabolic influence largely dictated primarily by genomic and possible non-genomic signaling, satellite cell activation, interaction with other anabolic signaling pathways, upregulation or downregulation of the androgen receptor, and potential roles in co-activators and transcriptional activity; (2) Differential influences of growth hormones depending on the "type" of the hormone being assayed and the magnitude of the physiological stress; (3) The exquisite regulation of IGF-1 by a family of binding proteins (IGFBPs 1-6), which can either stimulate or inhibit biological action depending on binding; and (4) Circadian patterning and newly discovered variants of glucocorticoid isoforms largely dictating glucocorticoid sensitivity and catabolic, muscle sparing, or pathological influence. The downstream integrated anabolic and catabolic mechanisms of these hormones not only affect the ability of skeletal muscle to generate force; they also have implications for pharmaceutical treatments, aging, and prevalent chronic conditions such as metabolic syndrome, insulin resistance, and hypertension. Thus, advances in our understanding of hormones that impact anabolic: catabolic processes have relevance for athletes and the general population, alike.

Dataset Information

Small is beautiful: insulin-like growth factors and their role in growth, development, and cancer.

Publications

Small is beautiful: insulin-like growth factors and their role in growth, development, and cancer.

Similar Datasets

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