TNF and cancer: This would be exacerbated via cancer cells upregulating osteoclast activity through other established pathways,[35, 36] releasing TGF‐β sequestered in the surrounding bone matrix and further flooding the microenvironment with TGF‐β.[37] Therefore, we speculate that a tipping point could be reached, with sufficient TGF‐β present to shut down the anti‐cancer TNF‐α mechanism locally, resulting in cancer cell proliferation, tumor growth and secretion of yet more TGF‐β, setting off a proliferative positive feedback loop.