Nat Commun: Oghidini, in conjunction with drug-resistant signal suppression, significantly improves the prognosm of EGFR mutant lung cancer.

Lung cancer is one of the leading causes of cancer-related death worldwide, with non-small cell lung cancer (NSCLC) accounting for 85% of lung cancer.
Immune checkpoint inhibitors (ICIs), including anti-PD-1 antibodies and anti-PD-L1 antibodies, have been approved for use in the treatment of advanced NSCLC and have been shown to cure even such patients.
osimertinib is the third EGFR-TKI, the third representative of the skin growth factor inhibitor tyrosine kinase inhibitor, which selectively inhibits mutant EGFR, such as L858R, T790M mutations, and EGFR missing exon No. 19.
Osetinib treatment can be more effective in patients with NSCLC with EGFR-TKI's incurable EGFR-TKI mutation, including gefitinib and erlotinib.
AXL low-expression tumor cells are more sensitive to oxytinibs but are often accompanied by drug resistance during treatment, the associated drug resistance mechanism is not clear.
In this way, the study aims to develop novel start-up therapies to prevent the production of access resistance and further improve the prognostics of patients with advanced EGFR-TKC mutations by analyzing the relevant drug resistance mechanisms after initial treatment of EGFR-TKIs.
Map of the potential mechanisms by which oxytinib induces FOXA1 and IGF-1R expression The researchers found that cells with low expression levels of AXL were more sensitive to oxytinib than cells with high expression levels of AXL in EGFR mutant lung cancer (EGFRmut-LC) cells, but Ohithini resistance appeared in a small number of populations.
this resistance is caused by an increase in the expression level of IGF-1R (insulin-like growth factor-1 receptor) and phosphate level, while the transcription factor FOXA1 regulates the expression and phosphateization of the receptor.
IGF-1R interacts with EGFR and bridging proteins Researchers have found that IGF-1R interacts with EGFR and bridging proteins (including Gab1 and IRS1) and restores survival signals when treated with oghitini.
transplant tumor experiment showed that transient inhibition of IGF-1R combined with continuous oghithini therapy can eradicate tumors and prevent tumor regeneration, the preventive effect continued until after the drug was stopped.
, the results showed that oghithinib treatment with appropriate inhibition of drug-resistant signals can significantly improve the prognosios of EGFR mutant lung cancer.
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