Targeting ROR1 in combination with osimertinib in EGFR mutant lung cancer cells

• DOI: 10.1016/j.yexcr.2021.112940
• Publication Date: 2021-11-19T15:29:18Z
• Authors: Nozomu Nakagawa; Noriko Miyake; Nobuaki Ochi; Hiromichi Yamane; Masami Takeyama; Yasunari Nagasaki; Tomoko Ikeda; Etsuko Yokota; Takuya Fukazawa; Hidekazu Nakanishi; Daijiro Harada; Katsuyuki Kiura; Nagio Takigawa
• Keywords: Osimertinib; ROR1

Lung cancer that exhibits epidermal growth factor receptor (EGFR) gene mutation is sensitive to EGFR-tyrosine kinase inhibitors (TKIs), such as osimertinib. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) may be involved in overcoming EGFR-TKI resistance. Growth inhibition, colony formation, apoptosis, and mRNA/protein levels in four osimertinib-sensitive and resistant cell lines transfected with small interfering RNA (siRNA) targeting ROR1 (siROR1) were evaluated. Cell growth and colony formation were suppressed and apoptosis was increased in all cell lines treated with siROR1. Although EGFR, AKT, and ERK phosphorylation were not suppressed in all cell lines, TGF-β2, AXL, CDH2, PARP1, PEG10, and TYMS mRNA expression levels were reduced. The combination of osimertinib with siROR1 was effective for the four cell lines, particularly in the two osimertinib-sensitive lines. In conclusion, targeting ROR1 in combination with osimertinib in EGFR mutant lung cancer may be a novel therapeutic option.