By a News Reporter-Staff News Editor at Cancer Gene Therapy Week -- Fresh data on Biotechnology are presented in a new report. According to news reporting originating in Kumamoto, Japan, by NewsRx journalists, research stated, "Activation of the epidermal growth factor receptor (EGFR) has been observed in many malignant tumors and its constitutive signal transduction facilitates the proliferation of tumors. EGFR-tyrosine kinase inhibitors, such as gefitinib, are widely used as a molecular-targeting agent for the inactivation of EGFR signaling and show considerable therapeutic effect in non-small cell lung cancers harboring activating EGFR mutations."
The news reporters obtained a quote from the research from Kumamoto University, "However, prolonged treatment inevitably produces tumors with additional gefitinib-resistant mutations in EGFR, which is a critical issue for current therapeutics. We aimed to characterize the distinct molecular response to gefitinib between the drug-resistant and drug-sensitive lung adenocarcinoma cells in order to learn about therapeutics based on the molecular information. From the quantitative PCR analysis, we found a specific increase in p14(ARF) expression in gefitinib-sensitive lung adenocarcinoma clones, which was absent in gefitinib-resistant clones. Moreover, mitochondria-targeted p14(ARF) triggered the most augmented apoptosis in both clones. We identified the amino acid residues spanning from 38 to 65 as a functional core of mitochondrial p14(ARF) (p14 38-65 a.a.), which reduced the mitochondrial membrane potential and caused caspase-9 activation. The synthesized peptide covering the p14 38-65 a.a. induced growth suppression of the gefitinib-resistant clones without affecting nonneoplastic cells. Notably, transduction of the minimized dose of the p14 38-65 peptide restored the response to gefitinib like that in the sensitive clones."
According to the news reporters, the research concluded: "These findings suggest that the region of p14(ARF) 38-65 a. a. is critical in the pharmacologic action of gefitinib against EGFR-mutated lung adenocarcinoma cells and has potential utility in the therapeutics of gefitinib-resistant cancers."
For more information on this research see: Antitumor Impact of p14(ARF) on Gefitinib-Resistant Non-Small Cell Lung Cancers. Molecular Cancer Therapeutics, 2013;12(8):1616-1628. Molecular Cancer Therapeutics can be contacted at: Amer Assoc Cancer Research, 615 Chestnut St, 17TH Floor, Philadelphia, PA 19106-4404, USA. (American Association for Cancer Research - www.aacr.com; Molecular Cancer Therapeutics - mct.aacrjournals.org/)
Our news correspondents report that additional information may be obtained by contacting K. Saito, Kumamoto University, Dept. of Immunol, Grad Sch Med Sci, Chuo Ku, Kumamoto, Japan. Additional authors for this research include N. Takigawa, N. Ohtani, H. Iioka, Y. Tomita, R. Ueda, J. Fukuoka, K. Kuwahara, E. Ichihara, K. Kiura and E. Kondo (see also technology.html">Biotechnology).
Keywords for this news article include: Asia, Antineoplastics, Biotechnology, Pharmaceuticals, Japan, Drugs, Kumamoto, Genetics, Oncology, Gefitinib, Lung Neoplasms, Adenocarcinomas, EGFR Inhibitors, Protein Kinases, Membrane Proteins, Cancer Gene Therapy, Phosphotransferases, Non-Small Cell Lung Cancer, Tyrosine Kinase Inhibitors
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