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Featured Clinical Reviews

June 1, 1994

Oncology and Hematology

Author Affiliations

National Cancer Institute, Bethesda, Md

JAMA. 1994;271(21):1693-1695. doi:10.1001/jama.1994.03510450065036

Cell division, differentiation, survival, and programmed death are determined by growth factor-triggered cascades of convergent signaling pathways. The function of a cell depends on molecular messages moving from the extracellular space across the cell membrane through the cytoplasm and into the nucleus, where those messages modulate net gene expression. At least two pivotal intracellular components are activated during the early steps of the signaling cascade: (1) protein tyrosine kinases (PTKs), some of which form the internal domains of many membrane-spanning growth factor receptors, others of which act within the cytoplasm, and all of which are commonly encoded by growth-promoting oncogenes, and (2) membrane-associated G proteins encoded by the ras family of oncogenes. Net overexpression or derangements of PTK-encoding oncogenes (eg, c-src, c-abl, c-kit, and the erb family) and ras serve as critical driving forces in the evolution of many epithelial and lymphohematopoietic cancers.

Many investigators have now demonstrated a crucial

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