Knockdown of PLAT enhances the anticancer effect of gefitinib in non-small cell lung cancer

Lung cancer is the leading cause of cancer incidence and mortality worldwide, with 1.8 million people diagnosed and 1.6 million deaths due to the disease annually (1). Non-small cell lung cancer (NSCLC) accounts for nearly 85% of all cases of lung cancer (2,3). Epidermal growth factor receptor (EGFR), an extensively studied protein that promotes tumor proliferation, angiogenesis, metastatic potential, and chemo-resistance and inhibits cell apoptosis, is highly expressed on the surface of NSCLC cells and commonly mutated (4,5). Nearly 90% of EFGR mutations in NSCLC patients are attributed to the deletion of exon 19 and the L858R substitution in exon 21 (6-8). Thus, tyrosine kinase inhibitors (TKIs) targeting EGFR, such as gefitinib and erlotinib, have become an efficient first-line anti-tumor approach for such patients. However, patients receiving TKI therapy inevitably develop resistance to these drugs after about 10–14 months. Mechanisms of resistance include additional EGFR mutations (T790M or Cys797Ser), c-MET amplification, human epidermal growth factor receptor 2 (HER2) amplification, epithelial-mesenchymal transition (EMT), small cell lung cancer transformation, or AXL activation (7-11). Meanwhile, other mechanisms of resistance remain to be discovered