SMAD2 and central nervous system cancer: Examples of TAM-produced growth factors, contributing to chemotherapy resistance, include TGF-β1, overproduced by M2 TAMs in glioma, which enhance stemness and resistance of glioma cells via the SMAD2/3 signaling pathway [54]; milk-fat globule epidermal growth factor-VIII (MFG-E8), discovered in TAMs of colon cancer and NSCLC, which activates STAT3; and Sonic Hedgehog signaling in tumor cells resulting in increased tumorigenicity and drug resistance [55].