In the TME, tumor cells secrete various cytokines, such as TGF-β (Caballero-Díaz et al., 2020) and PDGF (Kocabayoglu et al., 2015; Anderson and Simon, 2020), to promote the activation and proliferation of HSCs, and the activated HSCs (aHSCs) induce drug resistance and epithelial–mesenchymal transition (EMT) by producing pro-tumor factors such as HGF, IGF, and others (Camblin et al., 2018; Chen et al., 2021a; Östman, 2017; Rhee et al., 2018). This evidence concerns the gene IGF1 and neoplasm.