TGFB1 and cancer: First, whereas dysregulation of TGF-β signaling is recognized as the main driver of fibroblast-to-myofibroblast conversion in cancer, targeting this pathway is difficult due to its pleiotropic nature and carries the risk of adverse effects in patients; targeting a downstream mediator of TGF-β signaling such as SPHK1 should allow for more specific inhibition of the tumor-promoting aspects of TGF-β signaling [52, 53].