Druggable signaling proteins.
In normal cells, signaling pathways are tightly regulated. However, when they are aberrantly activated, certain pathways are capable of causing diseases. In many tumors, the aberrantly activated signaling proteins include members of the epidermal growth factor receptor family, the Ras proteins, protein kinase C isoenzymes, BCR-ABL fusion protein as well as transcription factors such as signal transducers and activators of transcriptions and Myc. Accordingly, deregulation of these signaling proteins holds promise for the development of new anticancer drugs. Studies in vitro and in disease-relevant models demonstrated that blocking the activation of a key target in a constitutively activated signaling pathway could reverse disease phenotype. Moreover, constitutive activation of the target alone is sufficient to induce relevant disease phenotype. Notably, the most dramatic therapeutic advances in cancer therapy during the last decade have come from agents targeted against active thyrosine kinases. These include imatinib (anti-BCR-ABL), gefitinib (anti-EGF receptor), and herpetin (anti-ErbB-2). Here, some selected validated and drugable targets are summarized.
Sioud
Mouldy
M
Department of Immunology, Institute for Cancer Research, The Norwegian Radium Hospital, University of Oslo, Oslo, Norway.
Leirdal
Marianne
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects*
D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors