Potential signaling and attenuation of radiation-induced lung fibrosis

Abstract

Purpose/Objective: Radiotherapy is a key component in the management of lung cancer. Unfortunately, radiotherapy is particularly toxic to the lung potentially inducing fatal pneumonitis and fibrosis in a radiation dose-dependent manner. The lung is therefore the major dose-limiting organ for radiotherapy of cancer in the thoracic region. The pathogenesis of radiation-induced lung injury at the molecular level is still unclear. Fibrosis is thought to represent the consequence of direct damage to local tissues and/or vascular endothelium by ionizing radiation and the simultaneous expression of proinflammatory and profibrotic cytokines. Studies suggest that growth factors for fibroblasts (including platelet-derived growth factor (PDGF), insulin-like growth factor I (IGF-I)) and cytokines stimulating collagen synthesis (notably transforming growth factor-beta TGF-b) are largely responsible for the fibrotic process. The purpose of this investigation was to evaluate the effects of a specific PDGF signaling inhibitor in vitro and in vivo in a fibrosis-sensitive mouse model for its ability to reduce fibrosis.