Bone-marrow-derived MSCs residing in the hypoxic solid cancer microenvironment produce high levels of molecules associated with adipocytes, including adipokine leptin and IGFBPs. It is suggested that leptin induces the resistance of lung cancer cells to erlotinib through activating IGF-1R signalling. IGFBP2 induces erlotinib resistance by activating IGF-1R signalling in an IGF-1-independent manner. IGFBP2 had a synergistic effect with leptin to induce erlotinib resistance in vitro and in vivo. The gene discussed is LEP; the disease is lung carcinoma.