American Association for Cancer Research
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15357163mct180179-sup-197149_2_supp_5153946_phwnq3.xlsx (21.52 kB)

Supplementary Data from The Secretome Engages STAT3 to Favor a Cytokine-rich Microenvironment in Mediating Acquired Resistance to FGFR Inhibitors

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posted on 2023-04-03, 15:01 authored by Xinyi Wang, Jing Ai, Hongyan Liu, Xia Peng, Hui Chen, Yi Chen, Yi Su, Aijun Shen, Xun Huang, Jian Ding, Meiyu Geng

Table S1. Lists of antibodies, small interference RNA sequences and inhibitors used in this study

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Natural Science Foundation of China

Research Program of the Chinese Academy of Sciences

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ARTICLE ABSTRACT

Acquired resistance severely hinders the application of small-molecule inhibitors. Our understanding of acquired resistance related to FGFRs is limited. Here, to explore the underlying mechanism of acquired resistance in FGFR-aberrant cancer cells, we generated cells resistant to multiple FGFR inhibitors (FGFRi) and investigated the potential mechanisms underlying acquired resistance. We discovered that reprogramming of the secretome is closely associated with acquired resistance to FGFRi. The secretome drives acquired resistance by activating the transcription factor STAT3 via its cognate receptors. Moreover, macrophages and fibroblasts could interact with cancer cells to enhance acquired resistance by promoting exaggerated and dynamic cytokine secretion, as well as STAT3 activation. We also found that Hsp90 and HDAC inhibitors could substantially and simultaneously suppress the proliferation of resistant cells, the secretion of multiple cytokines, and the activation of STAT3. Our study offers translational insights concerning the poor efficacy observed in patients with macrophage- and fibroblast-rich lung cancers and breast tumors after treatment with FGFRi in clinical trials.

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    Molecular Cancer Therapeutics

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