Drug resistance via feedback activation of stat3 in oncogene-addicted cancer cells (Cancer cell 26,207-221,2014)

報告日期: 2014/10/17
報告時間: 5:10/6:00
報告學生: 張昌華
講評老師: 張玲
附件下載: 下載[1419-1411983721-1.pdf] 

Drug Resistance via Feedback Activation of Stat3 in

Oncogene-Addicted Cancer Cells

Ho-June Lee, Guanglei Zhuang, Yi Cao, Pan Du, Hyo-Jin Kim, and Jeff Settleman

(Cancer Cell, August 2014, Vol.26, p.207-221)

Speaker: Chang-Hua Chang (張昌華)    Commentator: Dr. Christina Ling Chang(張玲)

2014/10/17 17:10-18:00

Room 602


   Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, such as gefitinib and

erlotinib, are effective for non-small cell lung cancer (NSCLC) with activating EGFR mutations.

However, in a NSCLC patients with EGFR mutant tumors, author found that high levels of STAT3 itself, as well as the ALPP, ATP2A3, RARRES1, IL-32, and CFB genes, which were significantly upregulated by Stat3 during erlotinib treatment, are associated with poor prognosis.

To verify whether cancer cells engaged feedback activation of Stat3, upon drug treatment, that

contribute to drug resistance via feedback mechanisms. Authors examined whether Stat3 activation affects the overall response of erlotinib and MEK inhibitor in oncogene-addicted lung cancer cells. Moreover, author found ponatinib (FGFRs and JAK1 inhibitor) significantly prevented drug-resistant colonies when combined with each RTK inhibitor and MEK inhibitor. These findings indicate that cotargeting FGFRs and JAK disrupts a RTK inhibitor-driven Stat3 feedback activation loop that contributes to drug resistance in a variety of RTK dependent- and K-RAS mutant- lung cancer cells. In future studies, authors will be required to determine precisely how Stat3 activation protects cancer cells from apoptosis following drug treatment, the ChIP-Seq analysis of Stat3 target genes suggests that several Stat3-regulated genes are associated

with poor prognosis of lung adenocarcinoma patients.



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