Cellular senescence and radiation-induced pulmonary fibrosis

Abstract

Radiation-induced pulmonary fibrosis (RIPF) is a serious treatment complication that affects about 9%-30% cancer patients receiving radiotherapy for thoracic tumors. RIPF is characterized by progressive and irreversible destruction of lung tissues and deterioration of lung function, which can compromise quality of life and eventually lead to respiratory failure and death. Unfortunately, the mechanisms by which radiation causes RIPF have not been well established nor has an effective treatment for RIPF been developed. Recently, an increasing body of evidence suggests that induction of senescence by radiation may play an important role in RIPF and clearance of senescent cells (SnCs) with a senolytic agent, small molecule that can selectively kill SnCs, has the potential to be developed as a novel therapeutic strategy for RIPF. This review discusses some of these new findings to promote further study on the role of cellular senescence in RIPF and the development of senolytic therapeutics for RIPF.

Conflict of interest statement

CONFLICTS OF INTEREST

G.Z. and D.Z. are inventors of a pending patent application for the development of BCL-xL targeted senolytic agents. D.Z. is a co–founder and an advisor of Unity that develops senolytic agents to treat various age-related diseases in humans.

Copyright © 2019 Elsevier Inc. All rights reserved.

Figures

Figure 1.

Cellular senescence – a double-edged sword in the fight against cancer with thoracic radiotherapy (RT). ROS, reactive oxygen species; SASP, senescence-associated secretary phenotype; RIPF, radiation-induced pulmonary fibrosis; and EMT, epithelial-mesenchymal transition.

Figure 2.

Hypothetic model of mechanisms by which cellular senescence contributes to radiation-induced pulmonary fibrosis (RIPF). AEC2, type II alveolar epithelial cells; ASC, alveolar stem cells; ROS, reactive oxygen species SASP, senescence-associated secretary phenotype; RT, thoracic radiotherapy