Review Article

Lung Pneumonitis and Fibrosis in Cancer Therapy: A Review on Cellular and Molecular Mechanisms

Author(s): Chaofeng Xu*, Zhongtu Shang and Masoud Najafi*

Volume 23, Issue 16, 2022

Published on: 04 October, 2022

Page: [1505 - 1525] Pages: 21

DOI: 10.2174/1389450123666220907144131

Price: $65


Fibrosis and pneumonitis are the most important side effects of lung tissue following cancer therapy. Radiotherapy and chemotherapy by some drugs, such as bleomycin, can induce pneumonitis and fibrosis. Targeted therapy and immunotherapy also may induce pneumonitis and fibrosis to a lesser extent compared to chemotherapy and radiotherapy. Activation of lymphocytes by immunotherapy or infiltration of inflammatory cells such as macrophages, lymphocytes, neutrophils, and mast cells following chemo/radiation therapy can induce pneumonitis. Furthermore, the polarization of macrophages toward M2 cells and the release of anti-inflammatory cytokines stimulate fibrosis. Lung fibrosis and pneumonitis may also be potentiated by some other changes such as epithelial-mesenchymal transition (EMT), oxidative stress, reduction/oxidation (redox) responses, renin-angiotensin system, and the upregulation of some inflammatory mediators such as a nuclear factor of kappa B (NF-κB), inflammasome, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). Damages to the lung vascular system and the induction of hypoxia also can induce pulmonary injury following chemo/radiation therapy. This review explains various mechanisms of the induction of pneumonitis and lung fibrosis following cancer therapy. Furthermore, the targets and promising agents to mitigate lung fibrosis and pneumonitis will be discussed.

Keywords: Chemotherapy, radiotherapy, lung, fibrosis, pneumonitis, EMT.

Graphical Abstract
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