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Single-Cell Analyses Reveal Diverse Mechanisms of Resistance to EGFR Tyrosine Kinase Inhibitors in Lung Cancer

Cancer Res. 2021-07; 
Yukie Kashima, Daisuke Shibahara, Ayako Suzuki, Kyoko Muto, Ikei S Kobayashi, David Plotnick, Hibiki Udagawa, Hiroki Izumi, Yuji Shibata, Kosuke Tanaka, Masanori Fujii, Akihiro Ohashi, Masahide Seki, Koichi Goto, Katsuya Tsuchihara, Yutaka Suzuki, Susumu S Kobayashi
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DNA Sequencing … pcDNA3.1+/C-(K)DYK-CD74, which encodes human CD74, was purchased from GenScript (#OHu19995). CD74 coding sequence was PCR-amplified using Pfu Turbo DNA polymerase (Agilent). PCR products were verified by sequencing and then ligated into the MIGR1 … Get A Quote

摘要

Tumor heterogeneity underlies resistance to tyrosine kinase inhibitors (TKI) in lung cancers harboring mutations. Previous evidence suggested that subsets of preexisting resistant cells are selected by EGFR-TKI treatment, or alternatively, that diverse acquired resistance mechanisms emerge from drug-tolerant persister (DTP) cells. Many studies have used bulk tumor specimens or subcloned resistant cell lines to identify resistance mechanism. However, intratumoral heterogeneity can result in divergent responses to therapies, requiring additional approaches to reveal the complete spectrum of resistance mechanisms. Using EGFR-TKI-resistant cell models and clinical specimens, we performed single-cell RNA-seq and si... More

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