Radiation-induced lung toxicity – cellular and molecular mechanisms of pathogenesis, management, and literature review

Abstract

Lung, breast, and esophageal cancer represent three common malignancies with high incidence and mortality worldwide. The management of these tumors critically relies on radiotherapy as a major part of multi-modality care, and treatment-related toxicities, such as radiation-induced pneumonitis and/or lung fibrosis, are important dose limiting factors with direct impact on patient outcomes and quality of life. In this review, we summarize the current understanding of radiation-induced pneumonitis and pulmonary fibrosis, present predictive factors as well as recent diagnostic and therapeutic advances. Novel candidates for molecularly targeted approaches to prevent and/or treat radiation-induced pneumonitis and pulmonary fibrosis are discussed.

Long and short non-coding RNA and radiation response: a review

“…36 From studies on radiotherapy patients treated for thoracic tumors, it is known that radiation induces acute pneumonitis and chronic pulmonary fibrosis in the late stage. 37 In the cardiovascular system, radiation can induce pericardial disease, fibrosis, coronary artery disease (CAD), valvular injury and cardiac conduction system injury. 38 Chronically, the accumulation of genetic abnormalities from radiation-induced DNA damage can result in the development of leukemia approximately 10 years after exposure or other solid tumors up to 30 years after exposure.…”

X-change symposium: status and future of modern radiation oncology—from technology to biology

“…Finally, deciphering the molecular pathways leading to radiation induced toxicity will ultimately open new doors for molecular approaches heading for an increased therapeutic gain [96].…”

Phagocytosis of Astaxanthin-Loaded Microparticles Modulates TGFβ Production and Intracellular ROS Levels in J774A.1 Macrophages

“…Approximately 50% of all cancer patients receives radiotherapy to kill cancer cells and, thus, control their growth and the spread of the disease [ 13 ]. Radiation-induced fibrosis (RIF) affects a significant proportion of cancer patients receiving radiotherapy, by some estimates one-quarter of patients [ 14 ]. RIF consists in an excessive accumulation of collagen and other extracellular matrix components in the skin, subcutaneous tissues, lung, breast, gastrointestinal and urinary tracts causing multiple symptoms that impact the life quality of the patients [ 14 ].…”

“…Radiation-induced fibrosis (RIF) affects a significant proportion of cancer patients receiving radiotherapy, by some estimates one-quarter of patients [ 14 ]. RIF consists in an excessive accumulation of collagen and other extracellular matrix components in the skin, subcutaneous tissues, lung, breast, gastrointestinal and urinary tracts causing multiple symptoms that impact the life quality of the patients [ 14 ]. RIF is initiated by direct radiation-induced cell damage and by indirect mechanisms which, in turn, involve the generation of reactive oxygen and nitrogen species (ROS and RNS, respectively) through water radiolysis and activation of nitric oxide synthase [ 15 ].…”