Key cancer cell signal transduction pathways as therapeutic targets.
Growth factor signals are propagated from the cell surface, through the action of transmembrane receptors, to intracellular effectors that control critical functions in human cancer cells, such as differentiation, growth, angiogenesis, and inhibition of cell death and apoptosis. Several kinases are involved in transduction pathways via sequential signalling activation. These kinases include transmembrane receptor kinases (e.g., epidermal growth factor receptor EGFR); or cytoplasmic kinases (e.g., PI3 kinase). In cancer cells, these signalling pathways are often altered and results in a phenotype characterized by uncontrolled growth and increased capability to invade surrounding tissue. Therefore, these crucial transduction molecules represent attractive targets for cancer therapy. This review will summarize current knowledge of key signal transduction pathways, that are altered in cancer cells, as therapeutic targets for novel selective inhibitors. The most advanced targeted agents currently under development interfere with function and expression of several signalling molecules, including the EGFR family; the vascular endothelial growth factor and its receptors; and cytoplasmic kinases such as Ras, PI3K and mTOR.
Bianco
Roberto
R
Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica, Università di Napoli Federico II, Via S. Pansini 5, 80131 Napoli, Italy.
Melisi
Davide
D
Ciardiello
Fortunato
F
Tortora
Giampaolo
G
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism*; D011905:Genes, ras / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism; D011494:Protein Kinases / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases
D000970:Antineoplastic Agents; D011494:Protein Kinases; C546842:MTOR protein, human; D066246:ErbB Receptors; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases