Epithelial–mesenchymal transition in chemoradiation‐induced lung damage: Mechanisms and potential treatment approaches

• Published in: Journal of biochemical and molecular toxicology 2024-08, Vol.38 (8), p.e23790-n/a
• Main Authors: Saadh, Mohamed J., Sharma, Pawan, Naser, Israa Habeeb, Kumar, Abhishek, Ravi Kumar, M., Rasulova, Irodakhon, Mohammed, Faraj, Allela, Omer Qutaiba B., Mohammed, Wathiq Kh, Ahmed, Nahed Mahmood, Al‐Ani, Ahmed Muzahem, Redhee, Ahmed Huseen
• Format: Article
• Language: English
• Subjects: AKT protein; Alkylating agents; Alkylation; Animals; Antitumor activity; Biological activity; Bleomycin; Cancer; Cancer therapies; Chemoradiotherapy; Chemoradiotherapy - adverse effects; Chemotherapy; Epigenetics; Epithelial-Mesenchymal Transition - drug effects; epithelial‐mesenchymal transition (EMT); Fibrosis; Humans; Immunosuppressive agents; Lung cancer; Lung diseases; Lung Injury - chemically induced; Lung Injury - etiology; Lung Injury - metabolism; Lung Injury - pathology; Lungs; Malignancy; Oxidative stress; Oxidative Stress - drug effects; Pneumonitis; Pulmonary fibrosis; Pulmonary Fibrosis - chemically induced; Pulmonary Fibrosis - etiology; Pulmonary Fibrosis - metabolism; Pulmonary Fibrosis - pathology; pulmonary injury; Radiation therapy; radiotherapy
• ISSN: 1095-6670; 1099-0461; 1099-0461
• DOI: 10.1002/jbt.23790

Pulmonary injury is one of the key restricting factors for the therapy of malignancies with chemotherapy or following radiotherapy for chest cancers. The lung is a sensitive organ to some severely toxic antitumor drugs, consisting of bleomycin and alkylating agents. Furthermore, treatment with radiotherapy may drive acute and late adverse impacts on the lung. The major consequences of radiotherapy and chemotherapy in the lung are pneumonitis and fibrosis. Pneumonitis may arise some months to a few years behind cancer therapy. However, fibrosis is a long‐term effect that appears years after chemo/or radiotherapy. Several mechanisms such as oxidative stress and severe immune reactions are implicated in the progression of pulmonary fibrosis. Epithelial–mesenchymal transition (EMT) is offered as a pivotal mechanism for lung fibrosis behind chemotherapy and radiotherapy. It seems that pulmonary fibrosis is the main consequence of EMT after chemo/radiotherapy. Several biological processes, consisting of the liberation of pro‐inflammatory and pro‐fibrosis molecules, oxidative stress, upregulation of nuclear factor of κB and Akt, epigenetic changes, and some others, may participate in EMT and pulmonary fibrosis behind cancer therapy. In this review, we aim to discuss how chemotherapy or radiotherapy may promote EMT and lung fibrosis. Furthermore, we review potential targets and effective agents to suppress EMT and lung fibrosis after cancer therapy. Mechanisms of transforming growth factor‐β liberation after cancer therapy and the induction of epithelial–mesenchymal transition in the lung.