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

Transforming growth factor beta (TGF beta) 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, TGF beta 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 TGF beta is an early and persistent event in irradiated tissues and that TGF beta signaling controls effective DNA damage response provides a new means to manipulate tumor response to radiation. Here we discuss preclinical studies unraveling TGF beta effects in cancer treatment and review TGF beta biology in lung cancer as an example of the opportunities for TGF beta pathway inhibition as a pharmaceutical approach to augment radiation therapy. Semin Radiat Oncol 23:242-251 Published by Elsevier Inc.