Drug insight: Small-molecule inhibitors of protein kinases in the treatment of thyroid cancer.
Molecular targeting of protein kinases is a new paradigm in the treatment of cancer. The clinical efficacy of low-molecular weight inhibitors of ABL, stem-cell growth-factor receptor, and the epidermal growth factor receptor in different tumor types is witness to the power of this approach. The presence of activating mutations of a kinase, or an increased gene copy number, might anticipate tumor responsiveness to its targeting. Thyroid cancer is the most prevalent endocrine malignancy and is frequently associated with the oncogenic conversion of two specific protein kinases, RET and BRAF. Small-molecule inhibitors of both kinases have already reached the clinical testing stage. Protein kinases other than RET and BRAF are also being evaluated for their potential in thyroid-cancer treatment.
Santoro
Massimo
M
Department of Cellular and Molecular Biology and Pathology L Califano, University Federico II, Naples, Italy. masantor@unina.it
Carlomagno
Francesca
F
D018263:Adenocarcinoma, Follicular / Q000209:etiology; D018276:Carcinoma, Medullary / Q000209:etiology; D002291:Carcinoma, Papillary / Q000209:etiology; D018390:Gene Targeting; D006801:Humans; D008954:Models, Biological; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D034622:RNA Interference; D013964:Thyroid Neoplasms / Q000188:drug therapy*
D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; C482119:BRAF protein, human; D017346:Protein Serine-Threonine Kinases; D048493:Proto-Oncogene Proteins B-raf