Gefitinib as targeted therapy for mucoepidermoid carcinoma of the lung: possible significance of CRTC1-MAML2 oncogene.
Recent reports of a clinical response to gefitinib in pulmonary mucoepidermoid carcinoma (MEC) in the absence of sensitizing EGFR mutations suggest that tyrosine kinase inhibitors (TKIs) may be effective in this tumor type. Although not documented in these reports, MEC of the lung may harbor a t(11;19) translocation with an associated novel fusion oncogene (CRTC1-MAML2). Furthermore, MECs arising in the salivary glands carry this mutation in a high proportion of cases. In vitro data has shown that MEC cell-lines with t(11;19) are sensitive to gefitinib and that this may be mediated by the action of CRTC1-MAML2 in up-regulating the EGFR ligand, amphiregulin. Data also shows that gefitinib demonstrates amphiregulin-dependant activity in NSCLC cell-lines. As such, it may be speculated that MEC from lung and salivary glands expressing CRTC1-MAML2 present a valid target for treatment with gefitinib, even in the absence of sensitizing EGFR mutations. Clinical studies are required to test this hypothesis.
O'Neill
Iain D
ID
D018277:Carcinoma, Mucoepidermoid / Q000188:drug therapy* / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
C500984:CRTC1 protein, human; D004268:DNA-Binding Proteins; C430872:MAML1 protein, human; D015514:Oncogene Proteins, Fusion; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D015534:Trans-Activators; D014157:Transcription Factors; D066246:ErbB Receptors; D000077156:Gefitinib