At the same time, tumor cells secrete more epithelial growth factors, fibroblast growth factor (FGF) and insulin-like growth factor (IGF), leading to a hypoxic, acidic, high interstitial fluid pressure (IFP) state in the microenvironment, which activates cancer associated fibroblasts (CAFs) to produce more matrix metalloproteinases (MMPs) and remodel the tumor extracellular matrices (ECM) [212]. The gene discussed is IGF1; the disease is neoplasm.