[A new strategy for treating small cell lung cancer].
Recent results from molecular biology have shown that lung cancer is characterized by multiple, sequentially appearing molecular changes that include genetic and epigenetic alterations. Among all types of lung cancer, small cell lung cancer (SCLC) is associated with the lowest rate of 5-year survival. In this symposium, we introduce our findings regarding the c-kit oncogenes in SCLC. We found that the c-kit gene is strongly expressed in SCLC. The c-kit gene was not expressed in normal bronchial epithelial cells, which indicates that this gene is abberantly transcribed in SCLC. In addition, c-kit-positive cases of SCLC showed autophosphorylation in response to recombinant human stem cell factor. Furthermore, adding rh stem cell factor of SCLC cell lines induced a significant chemotactic response and moderate in vitro cell growth. These results strongly suggest that abnormal expression of the c-kit gene may be involved in the pathogenesis of SCLC by autocrine/paracrine stimulation via the c-kit/SCF signal pathway. To overcome drug resistance, we assessed the efficacy of a chimeric toxin targeted to c-kit receptors.
Ueda
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R
Department of Internal Medicine II, Nagoya City University Medical School.
Takashi
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T
D018288:Carcinoma, Small Cell / Q000235:genetics / Q000628:therapy*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000235:genetics / Q000628:therapy*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D019089:Stem Cell Factor / Q000378:metabolism
D000922:Immunotoxins; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit