Moreover, the systemic administration of a combination of specific inhibitors of HIF-1α and TGF-βRI signalling elements, 2-methoxyestradiol plus SD-208, respectively, that target breast tumour cells and bone microenvironment, was also more effective at decreasing bone metastases of MDA-MB-231 breast cancer cells and osteoclastic bone resorption and stimulating the formation of bone mass than individual drugs [239]. The gene discussed is HIF1A; the disease is breast neoplasm.