MEK Inhibitor Trametinib combined with RTK Inhibitor Anlotinib in KRAS-Mutant Lung Cancer

Oncogenic KRAS mutations frequently detected in non-small cell lung cancer (NSCLC) have been considered undruggable until recent development of inhibitors, e.g., sortorasib, adagrasib or divarasib, specifically targeting KRASG12C. However, it still remains as a big challenge to target all the KRAS mutants besides KRASG12C. We here found that MEK inhibitor trametinib treatment results in the feedback activation of multiple receptor tyrosine kinases (RTKs) in NSCLC, and combined treatments with trametinib and anlotinib, a pan-RTK inhibitor, effectively inhibited KRAS-mutant lung cancer progression. For the combinational analysis, A549 cells were treated with trametinib (10nM) or anlotinib (1μM) or combination treatments for 24 hours in 6-well plates.