Tumors as Organs: Biologically Augmenting Radiation Therapy by Inhibiting Transforming Growth Factor β Activity in Carcinomas

Transforming growth factor β (TGFβ) plays critical roles in regulating a plethora of physiological processes in normal organs, including morphogenesis, embryonic development, stem cell differentiation, immune regulation, and wound healing. Though considered a tumor suppressor, TGFβ is a critical mediator of tumor microenvironment, in which it likewise mediates tumor and stromal cell phenotype, recruitment, inflammation, immune function, and angiogenesis. The fact that activation of TGFβ is an early and persistent event in irradiated tissues and that TGFβ signaling controls effective DNA damage response provides a new means to manipulate tumor response to radiation. Here we discuss preclinical studies unraveling TGFβ effects in cancer treatment and review TGFβ biology in lung cancer as an example of the opportunities for TGFβ pathway inhibition as a pharmaceutical approach to augment radiation therapy.