Although the resistance mechanism of lenvatinib in gastric cancer remains unclear, previous studies in HCC have demonstrated that CAF activation is strongly associated with lenvatinib resistance.[27] CAF‐derived secreted phosphoprotein 1 activates bypass signaling pathways in HCC cells, conferring resistance to TKI‐induced apoptosis and promoting tumor progression.[28] PGF is identified as a key protein associated with the treatment efficacy of lenvatinib plus paclitaxel in the DNB panel. Here, SPP1 is linked to gastric cancer.