Radical hemithoracic radiotherapy (RHR), after lung-sparing surgery, has recently become a concrete therapeutic option for malignant pleural mesothelioma (MPM), an asbestos-related, highly aggressive tumor with increasing incidence and poor prognosis. Although the toxicity associated to this treatment has been reduced, it is still not negligible and must be considered when treating patients. Genetic factors appear to play a role determining radiotherapy toxicity. The aim of this study is the identification of biological pathways, retrieved through whole exome sequencing (WES), possibly associated to the development of lung adverse effects in MPM patients treated with RHR. The study included individuals with MPM, treated with lung-sparing surgery and chemotherapy, followed by RHR with curative intent, and followed up prospectively for development of pulmonary toxicity. Due to the strong impact of grade 3 pulmonary toxicities on the quality of life, compared with less serious adverse events, for genetic analyses, patients were divided into a none or tolerable pulmonary toxicity (NoSTox) group (grade ≤2) and a severe pulmonary toxicity (STox) group (grade = 3). Variant enrichment analysis allowed us to identify different pathway signatures characterizing NoSTox and Stox patients, allowing to formulate hypotheses on the protection from side effects derived from radiotherapy as well as factors predisposing to a worst response to the treatment. Our findings, being aware of the small number of patients analyzed, could be considered a starting point for the definition of a panel of pathways, possibly helpful in the management of MPM patients.
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http://dx.doi.org/10.3389/fonc.2021.784081 | DOI Listing |
Int J Mol Sci
January 2025
Zayed Center for Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates.
While the pulmonary effects of regular waterpipe smoking (R-WPS) are well-defined, the impact of occasional waterpipe smoking (O-WPS) on the lungs remains less established. This study investigated the pulmonary toxicity and underlying mechanisms of O-WPS versus R-WPS following 6 months of exposure, focusing on histopathology, inflammation in the lung, bronchoalveolar lavage fluid (BALF), and plasma, as well as oxidative stress, genotoxicity, mitochondrial dysfunction, and the expression of mitogen-activated protein kinases (MAPKs) in lung homogenates. Exposure to both O-WPS and R-WPS resulted in significant histological changes, including increased numbers of alveolar macrophages and lymphocytes, as well as interstitial fibrosis.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Centro di Riferimento Oncologico di Aviano (CRO), Department of Medical Oncology, IRCCS, 33081 Aviano, Italy.
Since the discovery of the first-generation ALK inhibitor, many other tyrosine kinase inhibitors have been demonstrated to be effective in the first line or further lines of treatment in patients with advanced non-small cell lung cancer with EMLA4-ALK translocation. This review traces the main milestones in the treatment of ALK-positive metastatic patients and the survival outcomes in the first-line and second-line settings with different ALK inhibitors. It presents the two options available for first-line treatment at the present time: sequencing different ALK inhibitors versus using the most potent inhibitor in front-line treatment.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Oncology, University Hospital of Udine, 33100 Udine, Italy.
Antibody-drug conjugates (ADCs) represent one of the most promising and rapidly emerging anti-cancer therapies because they combine the cytotoxic effect of the conjugate payload and the high selectivity of the monoclonal antibody, which binds a specific membrane antigen expressed by the tumor cells. In non-small cell lung cancer (NSCLC), ADCs are being investigated targeting human epidermal growth factor receptor 2 (), human epidermal growth factor receptor 3 (), trophoblast cell surface antigen 2 (), Mesenchymal-epithelial transition factor (), and carcinoembryonic antigen-related cell adhesion molecule 5 (). To date, Trastuzumab deruxtecan is the only ADC that has been approved by the FDA for the treatment of patients with NSCLC, but several ongoing studies, both using ADCs as monotherapy and combined with other therapies, are investigating the efficacy of new ADCs.
View Article and Find Full Text PDFMolecules
January 2025
Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.
More than 70% of cancer patients receive radiotherapy during their treatment, with consequent various side effects on normal cells due to high ionizing radiation doses despite tumor shrinkage. To date, many radioprotectors and radiosensitizers have been investigated in preclinical studies, but their use has been hampered by the high toxicity to normal cells or poor tumor radiosensitization effects. Genistein is a naturally occurring isoflavone found in soy products.
View Article and Find Full Text PDFPhysiol Rep
January 2025
Department of Pathology and Pathophysiology, Medical College of Soochow University, Suzhou, Jiangsu, China.
Cisplatin is a widely used anticancer drug, but its accumulation in renal tubular epithelial cells (TECs) can cause acute kidney injury. Phosphoseryl-tRNA kinase (PSTK) is an intermediate product produced under oxidative stress conditions. This study aimed to elucidate whether PSTK could protect TECs and its possible mechanisms.
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