title: Targeted inhibition of kinases in cancer therapy.
abstract: With an understanding of the molecular changes that accompany cell transformation, cancer drug discovery has undergone a dramatic change in the past few years. Whereas most of the emphasis in the past has been placed on developing drugs that induce cell death based on mechanisms that do not discriminate between normal and tumor cells, recent strategies have emphasized targeting specific mechanisms that have gone awry in tumor cells. However, the identification of cancer-associated mutations in oncogenes and their amplification in tumors has suggested that inhibitors against such proteins might represent attractive substrates for targeted therapy. In the clinic, the success of imatinib (Gleevec®, STI571) and trastuzumab (Herceptin®), both firsts of their kind, spurred further development of new, second-generation drugs that target kinases in cancer. This review highlights a few important examples each of these types of therapies, along with some newer agents that are in various stages of development. Second-generation kinase inhibitors aimed at overriding emerging resistance to these therapies are also discussed.
authors.affiliation: Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Stacey J
authors.initials: SJ
authors.lastname: Baker
authors.forename: E Premkumar
authors.initials: EP
authors.lastname: Reddy
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000069439:Dasatinib; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib; D016313:Genes, abl / Q000187:drug effects / Q000235:genetics; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy; D058990:Molecular Targeted Therapy; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011494:Protein Kinases / Q000187:drug effects*; D011743:Pyrimidines / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use; D013844:Thiazoles / Q000627:therapeutic use; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011799:Quinazolines; D013844:Thiazoles; D000069347:Erlotinib Hydrochloride; D011494:Protein Kinases; C512478:EGFR protein, human; D066246:ErbB Receptors; C498826:nilotinib; D000068878:Trastuzumab; D000069439:Dasatinib; D000077156:Gefitinib