Mechanisms of Bleomycin-induced Lung Fibrosis: A Review of Therapeutic Targets and Approaches

• Published in: Cell biochemistry and biophysics 2024-09, Vol.82 (3), p.1845-1870
• Main Authors: Mohammed, Shaimaa M., Al-Saedi, Haider Falih Shamikh, Mohammed, Amjed Qasim, Amir, Ahmed Ali, Radi, Usama Kadem, Sattar, Ruaa, Ahmad, Irfan, Ramadan, Montather F., Alshahrani, Mohammad Y., Balasim, Halah Majeed, Alawadi, Ahmed
• Format: Article
• Language: English
• Subjects: Alveoli; Animals; Antibiotics, Antineoplastic - adverse effects; Anticancer properties; Antineoplastic drugs; Biochemistry; Biological and Medical Physics; Biomedical and Life Sciences; Biophysics; Biotechnology; Bleomycin; Bleomycin - adverse effects; Cancer; Cancer therapies; Cell Biology; Cell death; Cell proliferation; Cervical cancer; Disease management; Drug development; Epithelial cells; Epithelium; Fibroblasts; Fibrosis; Head & neck cancer; Humans; Immune system; Immunosuppressive agents; Life Sciences; Lung - drug effects; Lung - pathology; Lung cancer; Lung diseases; Lungs; Molecular modelling; Non-Hodgkin's lymphoma; Ovarian cancer; Oxidative stress; Oxidative Stress - drug effects; Pharmacology/Toxicology; Pneumonitis; Pulmonary Fibrosis - chemically induced; Pulmonary Fibrosis - drug therapy; Pulmonary Fibrosis - pathology; Review Paper; Side effects; Testicular cancer; Therapeutic targets; Toxicity
• ISSN: 1085-9195; 1559-0283; 1559-0283
• DOI: 10.1007/s12013-024-01384-9

Pulmonary toxicity is a serious side effect of some specific anticancer drugs. Bleomycin is a well-known anticancer drug that triggers severe reactions in the lungs. It is an approved drug that may be prescribed for the treatment of testicular cancers, Hodgkin’s and non-Hodgkin’s lymphomas, ovarian cancer, head and neck cancers, and cervical cancer. A large number of experimental studies and clinical findings show that bleomycin can concentrate in lung tissue, leading to massive oxidative stress, alveolar epithelial cell death, the proliferation of fibroblasts, and finally the infiltration of immune cells. Chronic release of pro-inflammatory and pro-fibrotic molecules by immune cells and fibroblasts leads to pneumonitis and fibrosis. Both fibrosis and pneumonitis are serious concerns for patients who receive bleomycin and may lead to death. Therefore, the management of lung toxicity following cancer therapy with bleomycin is a critical issue. This review explains the cellular and molecular mechanisms of pulmonary injury following treatment with bleomycin. Furthermore, we review therapeutic targets and possible promising strategies for ameliorating bleomycin-induced lung injury.