Originally published as JCO Early Release 10.1200/JCO.2005.23.648 on June 27 2005
Journal of Clinical Oncology, Vol 23, No 23 (August 10), 2005: pp. 5386-5403
© 2005 American Society of Clinical Oncology.
Intracellular Signal Transduction Pathway Proteins As Targets for Cancer Therapy
Alex A. Adjei,
Manuel Hidalgo
From the Mayo Clinic College of Medicine and Mayo Foundation, Departments of Oncology, Rochester, MN; and The Sidney Kimmel Cancer Center at The Johns Hopkins Hospital, Baltimore, MD
Address reprint requests to Alex A. Adjei, MD, PhD, Division of Medical Oncology, Mayo Clinic, 200 First St SW, Rochester, MN 55905; e-mail: adjei.alex{at}mayo.edu.
Circulating cytokines, hormones, and growth factors control all aspects of cell proliferation, differentiation, angiogenesis, apoptosis, and senescence. These chemical signals are propagated from the cell surface to intracellular processes via sequential kinase signaling, arranged in modules that exhibit redundancy and cross talk. This signal transduction system comprising growth factors, transmembrane receptor proteins, and cytoplasmic secondary messengers is often exploited to optimize tumor growth and metastasis in malignancies. Thus, it represents an attractive target for cancer therapy. This review will summarize current knowledge of selected intracellular signaling networks and their role in cancer therapy. The focus will be on pathways for which inhibitory agents are currently undergoing clinical testing. Original data for inclusion in this review were identified through a MEDLINE search of the literature. All papers from 1966 through March 2005 were identified by the following search terms: "signal transduction," "intracellular signaling," "kinases," "proliferation," "growth factors," and "cancer therapy." All original research and review papers related to the role of intracellular signaling in oncogenesis and therapeutic interventions relating to abnormal cell signaling were identified. This search was supplemented by a manual search of the Proceedings of the Annual Meetings of the American Association for Cancer Research, American Society of Clinical Oncology, and the American Association for Cancer Research (AARC) –European Organisation for Research and Treatment of Cancer (EORTC) –National Cancer Institute (NCI) Symposium on New Anticancer Drugs.
Terms in blue are defined in the glossary, found at the end of this issue and online at www.jco.org.
Authors' disclosures of potential conflicts of interest are found at the end of this article.
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