{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T05:47:10Z","timestamp":1768456030118,"version":"3.49.0"},"reference-count":56,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Oral tongue squamous cell carcinoma (OTSCC) is a common type of oral cancer influenced by genetic, epigenetic, and environmental factors like exposure to environmental toxins. These environmental toxins can decrease the effectiveness of established chemotherapy drugs, such as Irinotecan, used in OTSCC treatment. Bioinformatics, drug discovery, and machine learning techniques were employed to investigate the impact of Irinotecan on OTSCC patients by identifying targets and signaling pathways, including those that positively influence protein phosphorylation, protein tyrosine kinase activity, the PI3K-Akt (Phosphatidylinositol 3-kinase- Protein Kinase B) signaling system, cancer pathways, focal adhesion, and the HIF-1 (Hypoxia-Inducible Factor 1) signaling pathway. Later, the protein\u2013protein interactions (PPIs) network, along with twelve cytoHubba approaches to finding the most interacting molecule, was employed to find the important proteins BCL2 and EGFR. Drugs related to BCL2 and EGFR were extracted from the DGIdb database for further molecular docking. Molecular docking revealed that Docetaxel, Paclitaxel, Imatinib, Ponatinib, Ibrutinib, Sorafenib, and Etoposide showed more binding affinity than Irinotecan (i.e., \u22129.8, \u22129.6). Of these, Paclitaxel (\u221210.3, \u221211.4) and Imatinib (\u22129.9, \u221210.4) are common in targeting BCL2 and EGFR. Using these identified candidate genes and pathways, we may be able to uncover new therapeutic targets for the treatment of OTSCC. Furthermore, molecular dynamics (MD) simulations were performed for selected ligand\u2013receptor complexes, revealing stable binding interactions and favorable energetic profiles that supported the docking results and strengthened the reliability of the proposed drug repurposing strategy.<\/jats:p>","DOI":"10.3390\/biology14091174","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T08:23:38Z","timestamp":1756801418000},"page":"1174","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Environmental Hazards and Chemoresistance in OTSCC: Molecular Docking and Prediction of Paclitaxel and Imatinib as BCL2 and EGFR Inhibitors"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-1957-0285","authenticated-orcid":false,"given":"Nishant Kumar","family":"Singh","sequence":"first","affiliation":[{"name":"Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow 226028, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9041-0844","authenticated-orcid":false,"given":"Prankur","family":"Awasthi","sequence":"additional","affiliation":[{"name":"Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow 226028, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agrika","family":"Gupta","sequence":"additional","affiliation":[{"name":"Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow 226028, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nidhi","family":"Anand","sequence":"additional","affiliation":[{"name":"Department of Pathology, Dr. Ram Manohar Lohia Institute of Medical Science, Vibhuti Khand, Gomtinagar, Lucknow 226010, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5167-9154","authenticated-orcid":false,"given":"Balendu Shekher","family":"Giri","sequence":"additional","affiliation":[{"name":"Sustainability Cluster, University of Petroleum and Energy Studies (UPES), Dehradun 248007, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saba","family":"Hasan","sequence":"additional","affiliation":[{"name":"Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow 226028, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,2]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA A Cancer J. 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