Mechanisms and potential targets for prevention and treatment of normal tissue injury after radiation therapy.

The ability to optimize treatment for cancer based on individual risk assessment for normal tissue injury has important implications in oncology because more aggressive therapy may improve outcome in the treatment of advanced non-small cell lung cancer. To achieve this goal, a thorough understanding of the molecular mechanisms responsible for radiation-induced toxicity will be essential. Recent research has shown that ionizing radiation triggers a series of genetic and molecular events that may lead to chronic, persistent alterations in the microenvironment, producing an aberrant wound healing response. Disrupted epithelial-stromal cell communication may also contribute to impaired wound healing. As a result of an improved understanding of these fundamental biologic responses to radiation, new approaches to the treatment and prevention of normal tissue injury will focus on correcting these disturbed molecular processes. Herein, we will summarize recent developments in this field, with an emphasis on the lung.