INS and neoplasm: For instance, local angiogenic factors within the ECM, which promote tumor vascularization and alleviate tumor hypoxia, as well as endocrine factors like insulin/insulin-like growth factor and sex hormones (e.g., androgens, estrogens, progesterones), can significantly impact proliferative signaling (Chuffa et al., 2017; LeRoith and Roberts, 2003).