Role of TGFβ in regulation of the tumor microenvironment and drug delivery (review)

Deregulation of cell signaling homeostasis is a predominant feature of cancer initiation and progression. Transforming growth factor β (TGFβ) is a pleiotropic cytokine, which regulates numerous biological processes of various tissues in an autocrine and paracrine manner. Aberrant activity of TGFβ signaling is well known to play dual roles in cancer, depending on tumor stage and cellular context. The crucial roles of TGFβ in modulating the tumor microenvironment, its contribution to the accumulation of mechanical forces within the solid constituents of a tumor and its effects on the effective delivery of drugs are also becoming increasingly clear. In this review, we discuss the latest advances in the efforts to unravel the effects of TGFβ signaling in various components of the tumor microenvironment and how these influence the generation of forces and the efficacy of drugs. We also report the implications of tumor mechanics in cancer therapy and the potential usage of anti-TGFβ agents to enhance drug delivery and augment existing therapeutic approaches. These findings provide new insights towards the significance of targeting TGFβ pathway to enhance personalized tumor treatment.