Overview of rationale and clinical trials with signal transduction inhibitors in lung cancer.

Arteaga CL, Khuri F, Krystal G, Sebti S
Semin Oncol. 2002 29 (1 Suppl 4): 15-26

PMID: 11894010

Most cellular proto-oncogenes encode proteins that participate in signaling pathways by which cells receive and execute instructions that lead to mitogenesis, differentiation, lineage determination, cell migration, extracellular matrix production, and apoptosis, among others. These proto-oncogene protein products include transmembrane receptor tyrosine kinases and receptor substrates, serine/threonine kinases, receptor adaptor molecules, low-molecular-weight GTPases, and transcription factors that, when overexpressed or mutationally activated, can lead to cell transformation and tumor progression. The large number of oncogenic protein tyrosine kinases plus the rare presence of phosphotyrosine in nontransformed cells argue persuasively that tyrosine phosphorylation and activation of signaling molecules downstream from receptor tyrosine kinases are critical events in growth control and transformation and are, therefore, rational targets for anticancer molecular therapies. We will review some of the more recent treatment strategies in non-small cell and small cell lung cancer targeted to dysregulated signaling pathways that are causally associated with tumor maintenance and progression.

MeSH Terms (19)

Alkyl and Aryl Transferases Carcinoma, Non-Small-Cell Lung Carcinoma, Small Cell Cell Transformation, Neoplastic Clinical Trials as Topic Disease Progression Enzyme Inhibitors ErbB Receptors Farnesyltranstransferase Humans Lung Neoplasms Phosphorylation Proto-Oncogene Proteins Proto-Oncogene Proteins c-kit Receptor Protein-Tyrosine Kinases Research Design Signal Transduction Tyrosine Up-Regulation

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