{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:44:40Z","timestamp":1760060680182,"version":"build-2065373602"},"reference-count":115,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"COMPETE 2020\u2014Operational Programme for Competitiveness and Internationalization (POCI), Portugal 2020","award":["UIDB\/4255\/2020","IF\/00092\/2014\/CP1255\/CT0004","PRR-09\/C06-834I07\/2024.P11721","2024.18026.PEX"],"award-info":[{"award-number":["UIDB\/4255\/2020","IF\/00092\/2014\/CP1255\/CT0004","PRR-09\/C06-834I07\/2024.P11721","2024.18026.PEX"]}]},{"name":"FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecno-logia, in a framework of the projects in CINTESIS, R&amp;D Unit","award":["UIDB\/4255\/2020","IF\/00092\/2014\/CP1255\/CT0004","PRR-09\/C06-834I07\/2024.P11721","2024.18026.PEX"],"award-info":[{"award-number":["UIDB\/4255\/2020","IF\/00092\/2014\/CP1255\/CT0004","PRR-09\/C06-834I07\/2024.P11721","2024.18026.PEX"]}]},{"name":"FCT and FEDER (European Union)","award":["UIDB\/4255\/2020","IF\/00092\/2014\/CP1255\/CT0004","PRR-09\/C06-834I07\/2024.P11721","2024.18026.PEX"],"award-info":[{"award-number":["UIDB\/4255\/2020","IF\/00092\/2014\/CP1255\/CT0004","PRR-09\/C06-834I07\/2024.P11721","2024.18026.PEX"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Personalized medicine has gained an important relevance over the years with the development of targeted therapies, especially in cancer, adapted to the individual molecular tumour profiles. Accordingly, drug repurposing arises as a powerful strategy to identify and use drugs already approved for other conditions, offering advantages in terms of cost, development time, and safety. Src and Abl tyrosine kinases have been investigated as potential targets in oncology, being frequently implicated in tumour development and progression by promoting cell proliferation, migration, and angiogenesis. This review aims to provide a comprehensive overview of five tyrosine kinase inhibitors\u2014saracatinib, imatinib, PP2, nilotinib and, tirbanibulin\u2014that act on Src and\/or Abl. Their mechanisms of action, original therapeutic indications, and potential for repurposing in other diseases, such as lung cancer, will be discussed. Although clinical data for these drugs in lung cancer remain limited, preclinical and clinical studies suggest promising therapeutic potential, particularly in specific molecular subtypes. Overall, this review highlights the therapeutic potential of Src and Abl inhibitors beyond their original contexts and supports their possible role in lung cancer therapy, considering the disease\u2019s high heterogeneity and the growing applicability of personalized medicine.<\/jats:p>","DOI":"10.3390\/ph18101426","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T10:27:53Z","timestamp":1758623273000},"page":"1426","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Src and Abl as Therapeutic Targets in Lung Cancer: Opportunities for Drug Repurposing"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5324-8826","authenticated-orcid":false,"given":"Raquel","family":"Ramos","sequence":"first","affiliation":[{"name":"PerMed Research Group, RISE-Health, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"},{"name":"RISE-Health, Department of Pathology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"},{"name":"Molecular Diagnostics Laboratory, Unilabs Portugal, Centro Empresarial Lionesa Porto, 4465-671 Le\u00e7a do Balio, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0708-6874","authenticated-orcid":false,"given":"Carlos","family":"Sousa","sequence":"additional","affiliation":[{"name":"PerMed Research Group, RISE-Health, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"},{"name":"Molecular Diagnostics Laboratory, Unilabs Portugal, Centro Empresarial Lionesa Porto, 4465-671 Le\u00e7a do Balio, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1283-1042","authenticated-orcid":false,"given":"Nuno","family":"Vale","sequence":"additional","affiliation":[{"name":"PerMed Research Group, RISE-Health, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"},{"name":"RISE-Health, Department of Pathology, Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal"},{"name":"Laboratory of Personalized Medicine, Department of Community Medicine, Health Information and Decision (MEDCIDS), Faculty of Medicine, University of Porto, 4200-450 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/s41416-021-01633-1","article-title":"Artificial intelligence in oncology: Current applications and future perspectives","volume":"126","author":"Luchini","year":"2022","journal-title":"Br. J. Cancer"},{"key":"ref_2","first-page":"e67891","article-title":"A Review of the Regulatory Challenges of Personalized Medicine","volume":"16","author":"Dharani","year":"2024","journal-title":"Cureus"},{"key":"ref_3","first-page":"100860","article-title":"Personalized medicine: An alternative for cancer treatment","volume":"42","author":"Singh","year":"2024","journal-title":"Cancer Treat. Res. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Hoeben, A., Joosten, E.A.J., and Van Den Beuken-Van Everdingen, M.H.J. (2021). Personalized Medicine: Recent Progress in Cancer Therapy. Cancers, 13.","DOI":"10.3390\/cancers13020242"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"102019","DOI":"10.1016\/j.ctrv.2020.102019","article-title":"Review of precision cancer medicine: Evolution of the treatment paradigm","volume":"86","author":"Tsimberidou","year":"2020","journal-title":"Cancer Treat. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/s41573-021-00195-4","article-title":"Kinase drug discovery 20 years after imatinib: Progress and future directions","volume":"20","author":"Cohen","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Masucci, M., Karlsson, C., Blomqvist, L., and Ernberg, I. (2024). Bridging the Divide: A Review on the Implementation of Personalized Cancer Medicine. J. Pers. Med., 14.","DOI":"10.20944\/preprints202404.0950.v1"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Sha, C., and Lee, P.C. (2024). EGFR-Targeted Therapies: A Literature Review. J. Clin. Med., 13.","DOI":"10.3390\/jcm13216391"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1093\/bib\/bbx017","article-title":"A review of network-based approaches to drug repositioning","volume":"19","author":"Ghadiri","year":"2018","journal-title":"Brief. Bioinform."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1134\/S1068162023020139","article-title":"Drug Repurposing: An Effective Tool in Modern Drug Discovery","volume":"49","author":"Kulkarni","year":"2023","journal-title":"Russ. J. Bioorg. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/nrd.2018.168","article-title":"Drug repurposing: Progress, challenges and recommendations","volume":"18","author":"Pushpakom","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41392-024-01808-1","article-title":"Drug repurposing for cancer therapy","volume":"9","author":"Xia","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1093\/bmb\/ldaa045","article-title":"Repurposing approved drugs for cancer therapy","volume":"137","author":"Schein","year":"2021","journal-title":"Br. Med. Bull."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Hijazi, M.A., Gessner, A., and El-Najjar, N. (2023). Repurposing of Chronically Used Drugs in Cancer Therapy: A Chance to Grasp. Cancers, 15.","DOI":"10.3390\/cancers15123199"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e401","DOI":"10.1016\/j.clml.2018.06.018","article-title":"Multiple Myeloma Treatment in Real-world Clinical Practice: Results of a Prospective, Multinational, Noninterventional Study","volume":"18","author":"Mohty","year":"2018","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1007\/s11427-013-4487-z","article-title":"A drug from poison: How the therapeutic effect of arsenic trioxide on acute promyelocytic leukemia was discovered","volume":"56","author":"Rao","year":"2013","journal-title":"Sci. China Life Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1182\/blood-2019-01-894980","article-title":"Management of acute promyelocytic leukemia: Updated recommendations from an expert panel of the European LeukemiaNet","volume":"133","author":"Sanz","year":"2019","journal-title":"Blood"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1177\/1753193418805249","article-title":"The teratogenic effects of thalidomide on limbs","volume":"44","author":"Vargesson","year":"2019","journal-title":"J. Hand Surg."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Al Khzem, A.H., Gomaa, M.S., Alturki, M.S., Tawfeeq, N., Sarafroz, M., Alonaizi, S.M., Al Faran, A., Alrumaihi, L.A., Alansari, F.A., and Alghamdi, A.A. (2024). Drug Repurposing for Cancer Treatment: A Comprehensive Review. Int. J. Mol. Sci., 25.","DOI":"10.20944\/preprints202410.2321.v1"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/nrc3563","article-title":"Role of ABL family kinases in cancer: From leukaemia to solid tumours","volume":"13","author":"Greuber","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.tips.2011.11.002","article-title":"Targeting Src family kinases in anti-cancer therapies: Turning promise into triumph","volume":"33","author":"Zhang","year":"2012","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Bhanumathy, K.K., Balagopal, A., Vizeacoumar, F.S., Vizeacoumar, F.J., Freywald, A., and Giambra, V. (2021). Protein Tyrosine Kinases: Their Roles and Their Targeting in Leukemia. Cancers, 13.","DOI":"10.3390\/cancers13020184"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Eshaq, A.M., Flanagan, T.W., Hassan, S.Y., Al Asheikh, S.A., Al-Amoudi, W.A., Santourlidis, S., Hassan, S.L., Alamodi, M.O., Bendhack, M.L., and Alamodi, M.O. (2024). Non-Receptor Tyrosine Kinases: Their Structure and Mechanistic Role in Tumor Progression and Resistance. Cancers, 16.","DOI":"10.3390\/cancers16152754"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s12943-018-0788-y","article-title":"Role of Non Receptor Tyrosine Kinases in Hematological Malignances and its Targeting by Natural Products","volume":"17","author":"Siveen","year":"2018","journal-title":"Mol. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1517\/13543784.2010.499898","article-title":"Novel dual Src\/Abl inhibitors for hematologic and solid malignancies","volume":"19","author":"Schenone","year":"2010","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.trecan.2015.07.004","article-title":"The Emerging Role of ABL Kinases in Solid Tumors","volume":"1","author":"Wang","year":"2015","journal-title":"Trends Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7760","DOI":"10.1111\/febs.16197","article-title":"Src family kinases (SFKs): Critical regulators of microglial homeostatic functions and neurodegeneration in Parkinson\u2019s and Alzheimer\u2019s diseases","volume":"289","author":"Portugal","year":"2022","journal-title":"FEBS J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1083\/jcb.130.2.355","article-title":"c-Src regulates the simultaneous rearrangement of actin cytoskeleton, p190RhoGAP, and p120RasGAP following epidermal growth factor stimulation","volume":"130","author":"Chang","year":"1995","journal-title":"J. Cell Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7001","DOI":"10.1038\/sj.onc.1205859","article-title":"Roles of activated Src and Stat3 signaling in melanoma tumor cell growth","volume":"21","author":"Niu","year":"2002","journal-title":"Oncogene"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.12659\/MSM.906266","article-title":"Src Promotes Metastasis of Human Non-Small Cell Lung Cancer Cells through Fn14-Mediated NF-\u03baB Signaling","volume":"24","author":"Wang","year":"2018","journal-title":"Med. Sci. Monit."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s12964-021-00739-6","article-title":"Role of the ABL tyrosine kinases in the epithelial\u2013mesenchymal transition and the metastatic cascade","volume":"19","author":"Luttman","year":"2021","journal-title":"Cell Commun. Signal."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"612","DOI":"10.3892\/mmr.2020.11156","article-title":"c-Abl-mediated tyrosine phosphorylation of DNA damage response proteins and implications in important cellular functions (Review)","volume":"22","author":"Bohio","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1146\/annurev.immunol.22.012703.104753","article-title":"The BCR-ABL story: Bench to bedside and back","volume":"22","author":"Wong","year":"2004","journal-title":"Annu. Rev. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"799","DOI":"10.4155\/fmc.12.29","article-title":"An update on dual Src\/Abl inhibitors","volume":"4","author":"Musumeci","year":"2012","journal-title":"Future Med. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"107059","DOI":"10.1016\/j.phrs.2024.107059","article-title":"Properties of FDA-approved small molecule protein kinase inhibitors: A 2024 update","volume":"200","author":"Roskoski","year":"2024","journal-title":"Pharmacol. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7010","DOI":"10.1002\/anie.201311096","article-title":"Substrate Activity Screening with Kinases: Discovery of Small-Molecule Substrate-Competitive c-Src Inhibitors","volume":"53","author":"Breen","year":"2014","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Hong, J.-B., Wu, P.-Y., Qin, A., Huang, Y.-W., Tseng, K.-C., Lai, C.-Y., Chan, W.-K., Fang, J., Cutler, D.L., and Tsai, T.-F. (2022). Topical Tirbanibulin, a Dual Src Kinase and Tubulin Polymerization Inhibitor, for the Treatment of Plaque-Type Psoriasis: Phase I Results. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14102159"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1158\/1535-7163.MCT-20-0069","article-title":"Allosteric Inhibition of ABL Kinases: Therapeutic Potential in Cancer","volume":"19","author":"Jones","year":"2020","journal-title":"Mol. Cancer Ther."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Carofiglio, F., Trisciuzzi, D., Gambacorta, N., Leonetti, F., Stefanachi, A., and Nicolotti, O. (2020). Bcr-Abl Allosteric Inhibitors: Where We Are and Where We Are Going to. Molecules, 25.","DOI":"10.3390\/molecules25184210"},{"key":"ref_40","first-page":"100533","article-title":"Mechanisms and signaling pathways of tyrosine kinase inhibitor resistance in chronic myeloid leukemia: A comprehensive review","volume":"24","author":"Lahmouad","year":"2025","journal-title":"Leuk. Res. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"108876","DOI":"10.1016\/j.celrep.2021.108876","article-title":"Paradoxical activation of c-Src as a drug-resistant mechanism","volume":"34","author":"Higuchi","year":"2021","journal-title":"Cell Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2565","DOI":"10.1038\/s41388-018-0617-1","article-title":"Resistance to Src inhibition alters the BRAF-mutant tumor secretome to promote an invasive phenotype and therapeutic escape through a FAK>p130Cas>c-Jun signaling axis","volume":"38","author":"Kessler","year":"2019","journal-title":"Oncogene"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1002\/cbin.11000","article-title":"Tyrosine kinase inhibitor-induced IL-6\/STAT3 activation decreases sensitivity of EGFR-mutant non-small cell lung cancer to icotinib","volume":"42","author":"Wang","year":"2018","journal-title":"Cell Biol. Int."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"101081","DOI":"10.1016\/j.drup.2024.101081","article-title":"Concurrent inhibition of ALK and SRC kinases disrupts the ALK lung tumor cell proteome","volume":"74","author":"Ramos","year":"2024","journal-title":"Drug Resist. Updat."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/s41416-025-03058-6","article-title":"Co-targeting SRC overcomes resistance to BRAF inhibitors in colorectal cancer","volume":"133","author":"Llamas","year":"2025","journal-title":"Br. J. Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"7313","DOI":"10.1038\/sj.onc.1210543","article-title":"The tyrosine kinase Abl is required for Src-transforming activity in mouse fibroblasts and human breast cancer cells","volume":"26","author":"Sirvent","year":"2007","journal-title":"Oncogene"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1182\/blood-2002-01-0288","article-title":"Dual-specific Src and Abl kinase inhibitors, PP1 and CGP76030, inhibit growth and survival of cells expressing imatinib mesylate\u2013resistant Bcr-Abl kinases","volume":"101","author":"Warmuth","year":"2003","journal-title":"Blood"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Wang, W., Sun, Y., Liu, X., Kumar, S.K., Jin, F., and Dai, Y. (2022). Dual-Targeted Therapy Circumvents Non-Genetic Drug Resistance to Targeted Therapy. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.859455"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1593\/neo.10328","article-title":"SRC: A century of science brought to the clinic","volume":"12","author":"Aleshin","year":"2010","journal-title":"Neoplasia"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"6465","DOI":"10.1021\/jm060434q","article-title":"N-(5-chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5- (tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine, a novel, highly selective, orally available, dual-specific c-Src\/Abl kinase inhibitor","volume":"49","author":"Hennequin","year":"2006","journal-title":"J. Med. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Jha, V., Macchia, M., Tuccinardi, T., and Poli, G. (2020). Three-Dimensional Interactions Analysis of the Anticancer Target c-Src Kinase with Its Inhibitors. Cancers, 12.","DOI":"10.3390\/cancers12082327"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"8501693","DOI":"10.1155\/2016\/8501693","article-title":"Current Research Therapeutic Strategies for Alzheimer\u2019s Disease Treatment","volume":"2016","author":"Folch","year":"2016","journal-title":"Neural Plast."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1002\/ana.24394","article-title":"Fyn inhibition rescues established memory and synapse loss in Alzheimer mice","volume":"77","author":"Kaufman","year":"2015","journal-title":"Ann. Neurol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Ramos, R., and Vale, N. (2024). Dual Drug Repurposing: The Example of Saracatinib. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25084565"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1634\/theoncologist.2010-0408","article-title":"Current Status of Src Inhibitors in Solid Tumor Malignancies","volume":"16","author":"Puls","year":"2011","journal-title":"Oncologist"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"26090","DOI":"10.18632\/oncotarget.4636","article-title":"Src inhibitors act through different mechanisms in Non-Small Cell Lung Cancer models depending on EGFR and RAS mutational status","volume":"6","author":"Formisano","year":"2015","journal-title":"Oncotarget"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.cllc.2013.08.001","article-title":"A phase II trial of saracatinib, an inhibitor of src kinases, in previously-treated advanced non-small-cell lung cancer: The princess margaret hospital phase II consortium","volume":"15","author":"Laurie","year":"2014","journal-title":"Clin. Lung Cancer"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"S77","DOI":"10.1016\/S0959-8049(02)80607-4","article-title":"Imatinib: The first 3 years","volume":"38","author":"Capdeville","year":"2002","journal-title":"Eur. J. Cancer"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.str.2007.01.015","article-title":"c-Src Binds to the Cancer Drug Imatinib with an Inactive Abl\/c-Kit Conformation and a Distributed Thermodynamic Penalty","volume":"15","author":"Seeliger","year":"2007","journal-title":"Structure"},{"key":"ref_60","first-page":"114","article-title":"Imatinib Efficacy, Safety and Resistance in Iranian Patients with Chronic Myeloid Leukemia: A Review of Literature","volume":"15","author":"Amouei","year":"2021","journal-title":"Int. J. Hematol. Oncol. Stem Cell Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1002\/ajh.22076","article-title":"High-dose imatinib for newly diagnosed chronic phase chronic myeloid leukemia patients--systematic review and meta-analysis","volume":"86","author":"Leader","year":"2011","journal-title":"Am. J. Hematol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1007\/s12029-025-01210-2","article-title":"Neoadjuvant Imatinib in Recurrent\/Metastatic Gastrointestinal Stromal Tumors: A Systematic Review and Meta-analysis of Proportions","volume":"56","author":"Stavrou","year":"2025","journal-title":"J. Gastrointest. Cancer"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s10787-019-00656-8","article-title":"Imatinib modulates pro-inflammatory microenvironment with angiostatic effects in experimental lung carcinogenesis","volume":"28","author":"Puri","year":"2020","journal-title":"Inflammopharmacology"},{"key":"ref_64","first-page":"983","article-title":"Combination of SN-38 with gefitinib or imatinib overcomes SN-38-resistant small-cell lung cancer cells","volume":"17","author":"Takigawa","year":"2007","journal-title":"Oncol. Rep."},{"key":"ref_65","first-page":"33","article-title":"Combination of vitamin K2 plus imatinib mesylate enhances induction of apoptosis in small cell lung cancer cell lines","volume":"26","author":"Yokoyama","year":"2005","journal-title":"Int. J. Oncol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1158\/1535-7163.MCT-05-0503","article-title":"Imatinib inhibits c-Kit-induced hypoxia-inducible factor-1alpha activity and vascular endothelial growth factor expression in small cell lung cancer cells","volume":"5","author":"Litz","year":"2006","journal-title":"Mol. Cancer Ther."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3528","DOI":"10.1158\/1078-0432.CCR-0957-03","article-title":"Imatinib mesylate efficiently achieves therapeutic intratumor concentrations in vivo but has limited activity in a xenograft model of small cell lung cancer","volume":"10","author":"Wolff","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1093\/annonc\/mdi365","article-title":"A phase II trial of imatinib (ST1571) in patients with c-kit expressing relapsed small-cell lung cancer: A CALGB and NCCTG study","volume":"16","author":"Dy","year":"2005","journal-title":"Ann. Oncol."},{"key":"ref_69","first-page":"5880","article-title":"Phase II study of imatinib in patients with small cell lung cancer","volume":"9","author":"Johnson","year":"2003","journal-title":"Clin. Cancer Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"S49","DOI":"10.1016\/S0169-5002(03)00142-9","article-title":"Imatinib in small cell lung cancer","volume":"41","author":"Soria","year":"2003","journal-title":"Lung Cancer"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1097\/JTO.0b013e31814617b7","article-title":"Irinotecan, carboplatin, and imatinib in untreated extensive-stage small-cell lung cancer: A phase II trial of the Minnie Pearl Cancer Research Network","volume":"2","author":"Spigel","year":"2007","journal-title":"J. Thorac. Oncol."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Kellar, A., Egan, C., and Morris, D. (2015). Preclinical Murine Models for Lung Cancer: Clinical Trial Applications. Biomed Res. Int., 2015.","DOI":"10.1155\/2015\/621324"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.phrs.2018.05.002","article-title":"Imatinib prevents lung cancer metastasis by inhibiting M2-like polarization of macrophages","volume":"133","author":"Yao","year":"2018","journal-title":"Pharmacol. Res."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Oliveira, A., Moura, S., Pimentel, L., Neto, J., Dantas, R., Silva-Jr, F., Bastos, M., and Boechat, N. (2022). New Imatinib Derivatives with Antiproliferative Activity against A549 and K562 Cancer Cells. Molecules, 27.","DOI":"10.3390\/molecules27030750"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"869","DOI":"10.3892\/ijo_00000738","article-title":"Imatinib mesylate inhibits the proliferation-stimulating effect of human lung cancer-associated stromal fibroblasts on lung cancer cells","volume":"37","author":"Kinoshita","year":"2010","journal-title":"Int. J. Oncol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Bauman, J.E., Eaton, K.D., Wallace, S.G., Carr, L.L., Lee, S.J., Jones, D.V., Arias-Pulido, H., Cerilli, L.A., and Martins, R.G. (2012). A Phase II study of pulse dose imatinib mesylate and weekly paclitaxel in patients aged 70 and over with advanced non-small cell lung cancer. BMC Cancer, 12.","DOI":"10.1186\/1471-2407-12-449"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1097\/JTO.0b013e31822e7256","article-title":"Phase II trials of imatinib mesylate and docetaxel in patients with metastatic non-small cell lung cancer and head and neck squamous cell carcinoma","volume":"6","author":"Tsao","year":"2011","journal-title":"J. Thorac. Oncol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1002\/jcph.1312","article-title":"Clinical Pharmacokinetic and Pharmacodynamic Overview of Nilotinib, a Selective Tyrosine Kinase Inhibitor","volume":"58","author":"Tian","year":"2018","journal-title":"J. Clin. Pharmacol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1038\/s41375-020-01111-2","article-title":"Long-term outcomes with frontline nilotinib versus imatinib in newly diagnosed chronic myeloid leukemia in chronic phase: ENESTnd 10-year analysis","volume":"35","author":"Kantarjian","year":"2021","journal-title":"Leukemia"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1002\/ajh.27443","article-title":"Chronic myeloid leukemia: 2025 update on diagnosis, therapy, and monitoring","volume":"99","author":"Jabbour","year":"2024","journal-title":"Am. J. Hematol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"5910","DOI":"10.1158\/1078-0432.CCR-09-0542","article-title":"A phase I study of single-agent nilotinib or in combination with imatinib in patients with imatinib-resistant gastrointestinal stromal tumors","volume":"15","author":"Demetri","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1634\/theoncologist.2015-0161","article-title":"Phase II Trial of Nilotinib in Patients With Metastatic Malignant Melanoma Harboring KIT Gene Aberration: A Multicenter Trial of Korean Cancer Study Group (UN10-06)","volume":"20","author":"Lee","year":"2015","journal-title":"Oncologist"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"S20","DOI":"10.1053\/j.seminoncol.2011.01.015","article-title":"Clinical experience to date with nilotinib in gastrointestinal stromal tumors","volume":"38","author":"Reichardt","year":"2011","journal-title":"Semin. Oncol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.1007\/s00204-014-1385-5","article-title":"Combination therapy with nilotinib for drug-sensitive and drug-resistant BCR-ABL-positive leukemia and other malignancies","volume":"88","author":"Weisberg","year":"2014","journal-title":"Arch. Toxicol."},{"key":"ref_85","first-page":"4201727","article-title":"Dual EGFR and ABL Tyrosine Kinase Inhibitor Treatment in a Patient with Concomitant EGFR-Mutated Lung Adenocarcinoma and BCR-ABL1-Positive CML","volume":"2020","author":"Watanabe","year":"2020","journal-title":"Case Rep. Oncol. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2124","DOI":"10.1158\/1078-0432.CCR-24-3049","article-title":"A Phase I Study of Nilotinib in Combination with Paclitaxel in Patients with Advanced Solid Tumors","volume":"31","author":"Shin","year":"2025","journal-title":"Clin. Cancer Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1177\/15353702221139183","article-title":"c-Src inhibitor PP2 inhibits head and neck cancer progression through regulation of the epithelial-mesenchymal transition","volume":"248","author":"Lee","year":"2023","journal-title":"Exp. Biol. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1002\/hed.27216","article-title":"Src family kinase targeting in head and neck tumor cells using SU6656, PP2 and dasatinib","volume":"45","author":"Vu","year":"2023","journal-title":"Head. Neck"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"110948","DOI":"10.1016\/j.intimp.2023.110948","article-title":"PP2 alleviates the progression of osteoarthritis by inhibiting Wnt\/\u03b2-catenin and activating TGF-\u03b2\/Smad signaling","volume":"124","author":"Zhang","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_90","first-page":"2430","article-title":"Src family kinase inhibitor PP2 restores the E-cadherin\/catenin cell adhesion system in human cancer cells and reduces cancer metastasis","volume":"8","author":"Nam","year":"2002","journal-title":"Clin. Cancer Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1111\/cas.13572","article-title":"c-Src inhibitor selectively inhibits triple-negative breast cancer overexpressed Vimentin in vitro and in vivo","volume":"109","author":"Lou","year":"2018","journal-title":"Cancer Sci."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Yang, Y., Tang, N., Liu, Y., Choi, W., Kim, J.H., Kim, H.G., Yu, T., and Cho, J.Y. (2024). PP2 suppresses proliferation and migration of C6 Glioma and MDA-MB-231 cells by targeting both fibroblast growth factor receptor 1 and Src. Chem.-Biol. Interact., 403.","DOI":"10.1016\/j.cbi.2024.111252"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1158\/1078-0432.CCR-1565-02","article-title":"Combination of an SRC kinase inhibitor with a novel pharmacological antagonist of the urokinase receptor diminishes in vitro colon cancer invasiveness","volume":"10","author":"Boyd","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.leukres.2014.05.019","article-title":"Src family kinase inhibitor PP2 enhances differentiation of acute promyelocytic leukemia cell line induced by combination of all-trans-retinoic acid and arsenic trioxide","volume":"38","author":"Jung","year":"2014","journal-title":"Leuk. Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"687","DOI":"10.4143\/crt.2014.320","article-title":"The Effect of Chemoradiotherapy with SRC Tyrosine Kinase Inhibitor, PP2 and Temozolomide on Malignant Glioma Cells In Vitro and In Vivo","volume":"48","author":"Eom","year":"2016","journal-title":"Cancer Res. Treat."},{"key":"ref_96","first-page":"5059","article-title":"Src kinase inhibitor PP2 regulates the biological characteristics of A549 cells via the PI3K\/Akt signaling pathway","volume":"16","author":"Dai","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_97","first-page":"797","article-title":"SRC kinase inhibitor PP2 inhibits invasion and metastasis of lung cancer A549 cells by upregulating connexin43 expression","volume":"39","author":"Wang","year":"2019","journal-title":"Nan Fang. Yi Ke Da Xue Xue Bao"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1002\/cpdd.1024","article-title":"Tirbanibulin: A New Topical Therapy for Actinic Keratoses With a Novel Mechanism of Action and Improved Ease of Use","volume":"10","author":"Gilchrest","year":"2021","journal-title":"Clin. Pharmacol. Drug Dev."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1007\/s00403-024-02839-y","article-title":"Systematic review of randomized controlled trials of topicals for actinic keratosis field therapy","volume":"316","author":"Patel","year":"2024","journal-title":"Arch. Dermatol. Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2495","DOI":"10.2147\/CCID.S374122","article-title":"Tirbanibulin for Actinic Keratosis: Insights into the Mechanism of Action","volume":"15","author":"Schlesinger","year":"2022","journal-title":"Clin. Cosmet. Investig. Dermatol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1007\/s40265-021-01479-0","article-title":"Tirbanibulin: First Approval","volume":"81","author":"Markham","year":"2021","journal-title":"Drugs"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"4704","DOI":"10.1021\/acs.jmedchem.8b00164","article-title":"Discovery of Novel Dual Mechanism of Action Src Signaling and Tubulin Polymerization Inhibitors (KX2-391 and KX2-361)","volume":"61","author":"Smolinski","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1007\/s10637-013-9929-8","article-title":"A phase I trial of KX2-391, a novel non-ATP competitive substrate-pocket- directed SRC inhibitor, in patients with advanced malignancies","volume":"31","author":"Naing","year":"2013","journal-title":"Investig. New Drugs"},{"key":"ref_104","unstructured":"Ferlay, J., Ervik, M., Lam, F., Laversanne, M., Colombet, M., Mery, L., Pi\u00f1eros, M., Znaor, A., Soerjomataram, I., and Bray, F. (2025, August 07). Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available online: https:\/\/gco.iarc.who.int\/today."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e001021","DOI":"10.1136\/esmoopen-2020-001021","article-title":"Lung cancer symptoms at diagnosis: Results of a nationwide registry study","volume":"5","author":"Provencio","year":"2020","journal-title":"ESMO Open"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1177\/0141076819843654","article-title":"Lung cancer in never-smokers: A hidden disease","volume":"112","author":"Bhopal","year":"2019","journal-title":"J. R. Soc. Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1158\/1055-9965.EPI-19-0221","article-title":"Cancer Progress and Priorities: Lung Cancer","volume":"28","author":"Schabath","year":"2019","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"230190","DOI":"10.1183\/20734735.0190-2023","article-title":"Lung cancer screening: Where do we stand?","volume":"20","author":"Hardavella","year":"2024","journal-title":"Breathe"},{"key":"ref_109","first-page":"50","article-title":"Screening for lung cancer: 2023 guideline update from the American Cancer Society","volume":"74","author":"Wolf","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"981","DOI":"10.7150\/ijms.34739","article-title":"Molecular heterogeneity in lung cancer: From mechanisms of origin to clinical implications","volume":"16","author":"Bianco","year":"2019","journal-title":"Int. J. Med. Sci."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"704","DOI":"10.3390\/curroncol30010055","article-title":"Drug Repurposing in Non-Small Cell Lung Carcinoma: Old Solutions for New Problems","volume":"30","author":"Doumat","year":"2023","journal-title":"Curr. Oncol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1158\/1078-0432.CCR-14-1429","article-title":"Translational Implications of Tumor Heterogeneity","volume":"21","author":"Quezada","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Ramos, R., Moura, C.S., Costa, M., Lamas, N.J., Correia, R., Garcez, D., Pereira, J.M., Lindahl, T., Sousa, C., and Vale, N. (2025). Lung Cancer Therapy: The Role of Personalized Medicine. Cancers, 17.","DOI":"10.3390\/cancers17050725"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"651","DOI":"10.2174\/187152007784111278","article-title":"SRC family nonreceptor tyrosine kinases as molecular targets for cancer therapy","volume":"7","author":"Johnson","year":"2007","journal-title":"Anticancer Agents Med. Chem."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"e89647","DOI":"10.1172\/jci.insight.89647","article-title":"Inactivation of ABL kinases suppresses non-small cell lung cancer metastasis","volume":"1","author":"Gu","year":"2016","journal-title":"JCI Insight"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/10\/1426\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:47:33Z","timestamp":1760035653000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/10\/1426"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,23]]},"references-count":115,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["ph18101426"],"URL":"https:\/\/doi.org\/10.3390\/ph18101426","relation":{},"ISSN":["1424-8247"],"issn-type":[{"type":"electronic","value":"1424-8247"}],"subject":[],"published":{"date-parts":[[2025,9,23]]}}}