{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T10:39:18Z","timestamp":1792147158579,"version":"4.4.0"},"reference-count":160,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T00:00:00Z","timestamp":1719360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lung cancer is a leading cause of cancer-related morbidity and mortality worldwide. Metastases in the brain are a common hallmark of advanced stages of the disease, contributing to a dismal prognosis. Lung cancer can be broadly classified as either small cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC). NSCLC represents the most predominant histology subtype of lung cancer, accounting for the majority of lung cancer cases. Recent advances in molecular genetics, coupled with innovations in small molecule drug discovery strategies, have facilitated both the molecular classification and precision targeting of NSCLC based on oncogenic driver mutations. Furthermore, these precision-based strategies have demonstrable efficacy across the blood\u2013brain barrier, leading to positive outcomes in patients with brain metastases. This review provides an overview of the clinical features of lung cancer brain metastases, as well as the molecular mechanisms that drive NSCLC oncogenesis. We also explore how precision medicine-based strategies can be leveraged to improve NSCLC brain metastases.<\/jats:p>","DOI":"10.3390\/ijms25136961","type":"journal-article","created":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T05:11:39Z","timestamp":1719465099000},"page":"6961","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["A Review of the Molecular Determinants of Therapeutic Response in Non-Small Cell Lung Cancer Brain Metastases"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3020-2346","authenticated-orcid":false,"given":"Catherine","family":"Boldig","sequence":"first","affiliation":[{"name":"Department of Neurology, University of South Florida, 2 Tampa General Circle, Tampa, FL 33606, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4644-1149","authenticated-orcid":false,"given":"Kimberly","family":"Boldig","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Florida Jacksonville, 655 W. 8th St., Jacksonville, FL 32209, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sepideh","family":"Mokhtari","sequence":"additional","affiliation":[{"name":"Moffitt Cancer Center, Department of Neuro-Oncology, 12902 USF Magnolia Drive, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9656-4702","authenticated-orcid":false,"given":"Arnold B.","family":"Etame","sequence":"additional","affiliation":[{"name":"Moffitt Cancer Center, Department of Neuro-Oncology, 12902 USF Magnolia Drive, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ccm.2019.10.001","article-title":"Lung Cancer 2020: Epidemiology, Etiology, and Prevention","volume":"41","author":"Bade","year":"2020","journal-title":"Clin. Chest Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Souza, V.G.P., de Araujo, R.P., Santesso, M.R., Seneda, A.L., Minutentag, I.W., Felix, T.F., Hamamoto Filho, P.T., Pewarchuk, M.E., Brockley, L.J., and Marchi, F.A. (2023). Advances in the Molecular Landscape of Lung Cancer Brain Metastasis. Cancers, 15.","DOI":"10.3390\/cancers15030722"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13045-020-01025-7","article-title":"MEK inhibitors for the treatment of non-small cell lung cancer","volume":"14","author":"Han","year":"2021","journal-title":"J. Hematol. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5983","DOI":"10.1038\/s41467-022-33365-y","article-title":"The spatial transcriptomic landscape of non-small cell lung cancer brain metastasis","volume":"13","author":"Zhang","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1007\/s13402-017-0345-5","article-title":"Lung cancer-associated brain metastasis: Molecular mechanisms and therapeutic options","volume":"40","author":"Yousefi","year":"2017","journal-title":"Cell Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1097\/CM9.0000000000002127","article-title":"Tumor microenvironment in lung cancer-derived brain metastasis","volume":"135","author":"Liu","year":"2022","journal-title":"Chin. Med. J."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Tan, A.C., Itchins, M., and Khasraw, M. (2020). Brain Metastases in Lung Cancers with Emerging Targetable Fusion Drivers. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041416"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.1016\/j.athoracsur.2005.06.071","article-title":"Patterns of surgical care of lung cancer patients","volume":"80","author":"Little","year":"2005","journal-title":"Ann. Thorac. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1007\/s00408-020-00407-5","article-title":"Update 2020: Management of Non-Small Cell Lung Cancer","volume":"198","author":"Alexander","year":"2020","journal-title":"Lung"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"563","DOI":"10.21037\/tlcr.2016.10.16","article-title":"Epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of central nervous system metastases from non-small cell lung cancer: The present and the future","volume":"5","author":"Proto","year":"2016","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2466","DOI":"10.1093\/annonc\/mdr003","article-title":"Pemetrexed and cisplatin as first-line chemotherapy for advanced non-small-cell lung cancer (NSCLC) with asymptomatic inoperable brain metastases: A multicenter phase II trial (GFPC 07-01)","volume":"22","author":"Barlesi","year":"2011","journal-title":"Ann. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1159\/000066520","article-title":"Front-line paclitaxel\/cisplatin-based chemotherapy in brain metastases from non-small-cell lung cancer","volume":"64","author":"Cortes","year":"2003","journal-title":"Oncology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/S0169-5002(98)00021-X","article-title":"Chemotherapy with cisplatin and teniposide for cerebral metastases in non-small cell lung cancer","volume":"20","author":"Minotti","year":"1998","journal-title":"Lung Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1159\/000012185","article-title":"Combination chemotherapy of cisplatin, ifosfamide, and irinotecan with rhG-CSF support in patients with brain metastases from non-small cell lung cancer","volume":"59","author":"Fujita","year":"2000","journal-title":"Oncology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1002\/(SICI)1097-0142(19990401)85:7<1599::AID-CNCR23>3.0.CO;2-#","article-title":"Front-line chemotherapy with cisplatin and etoposide for patients with brain metastases from breast carcinoma, nonsmall cell lung carcinoma, or malignant melanoma: A prospective study","volume":"85","author":"Franciosi","year":"1999","journal-title":"Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/0959-8049(95)00507-2","article-title":"A phase II trial of fotemustine and cisplatin in central nervous system metastases from non-small cell lung cancer","volume":"32A","author":"Cotto","year":"1996","journal-title":"Eur. J. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1081\/CNV-120001173","article-title":"First-line chemotherapy with vinorelbine, gemcitabine, and carboplatin in the treatment of brain metastases from non-small-cell lung cancer: A phase II study","volume":"20","author":"Bernardo","year":"2002","journal-title":"Cancer Invest."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1023\/A:1008338312647","article-title":"Results of a phase III study of early versus delayed whole brain radiotherapy with concurrent cisplatin and vinorelbine combination in inoperable brain metastasis of non-small-cell lung cancer: Groupe Francais de Pneumo-Cancerologie (GFPC) Protocol 95-1","volume":"12","author":"Robinet","year":"2001","journal-title":"Ann. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1093\/neuonc\/nos004","article-title":"Upfront association of carboplatin plus pemetrexed in patients with brain metastases of lung adenocarcinoma","volume":"14","author":"Bailon","year":"2012","journal-title":"Neuro Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1200\/JCO.2009.24.0333","article-title":"Randomized phase III trial of vinorelbine plus cisplatin compared with observation in completely resected stage IB and II non-small-cell lung cancer: Updated survival analysis of JBR-10","volume":"28","author":"Butts","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/S1470-2045(06)70804-X","article-title":"Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): A randomised controlled trial","volume":"7","author":"Douillard","year":"2006","journal-title":"Lancet Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3552","DOI":"10.1200\/JCO.2007.13.9030","article-title":"Lung adjuvant cisplatin evaluation: A pooled analysis by the LACE Collaborative Group","volume":"26","author":"Pignon","year":"2008","journal-title":"J. Clin. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1080\/14737140.2018.1409624","article-title":"Role of chemotherapy and targeted therapy in early-stage non-small cell lung cancer","volume":"18","author":"Nagasaka","year":"2018","journal-title":"Expert. Rev. Anticancer. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Inamura, K. (2017). Lung Cancer: Understanding Its Molecular Pathology and the 2015 WHO Classification. Front. Oncol., 7.","DOI":"10.3389\/fonc.2017.00193"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s11060-012-0890-8","article-title":"E-cadherin as a predictive marker of brain metastasis in non-small-cell lung cancer, and its regulation by pioglitazone in a preclinical model","volume":"109","author":"Yoo","year":"2012","journal-title":"J. Neurooncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1158\/1078-0432.CCR-08-2124","article-title":"The expression of three genes in primary non-small cell lung cancer is associated with metastatic spread to the brain","volume":"15","author":"Ofek","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.lungcan.2013.03.011","article-title":"Vimentin expression predicts the occurrence of metastases in non small cell lung carcinomas","volume":"81","author":"Dauphin","year":"2013","journal-title":"Lung Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e1172153","DOI":"10.1080\/2162402X.2016.1172153","article-title":"Embracing rejection: Immunologic trends in brain metastasis","volume":"5","author":"Farber","year":"2016","journal-title":"Oncoimmunology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1038\/s41568-019-0224-7","article-title":"Brain immunology and immunotherapy in brain tumours","volume":"20","author":"Sampson","year":"2020","journal-title":"Nat. Rev. Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Morotti, A., Gentile, F., Lopez, G., Passignani, G., Valenti, L., Locatelli, M., Caroli, M., Fanizzi, C., Ferrero, S., and Vaira, V. (2023). Epigenetic Rewiring of Metastatic Cancer to the Brain: Focus on Lung and Colon Cancers. Cancers, 15.","DOI":"10.3390\/cancers15072145"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1038\/s43018-022-00361-6","article-title":"KMT2C deficiency promotes small cell lung cancer metastasis through DNMT3A-mediated epigenetic reprogramming","volume":"3","author":"Na","year":"2022","journal-title":"Nat. Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.20892\/j.issn.2095-3941.2022.0540","article-title":"Targeting the EGF receptor family in non-small cell lung cancer-increased complexity and future perspectives","volume":"19","author":"Boch","year":"2022","journal-title":"Cancer Biol. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1038\/nm.3388","article-title":"The quest to overcome resistance to EGFR-targeted therapies in cancer","volume":"19","author":"Chong","year":"2013","journal-title":"Nat. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"78985","DOI":"10.18632\/oncotarget.12587","article-title":"The prevalence of EGFR mutation in patients with non-small cell lung cancer: A systematic review and meta-analysis","volume":"7","author":"Zhang","year":"2016","journal-title":"Oncotarget"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"423","DOI":"10.2147\/CLEP.S69718","article-title":"Prevalence and natural history of ALK positive non-small-cell lung cancer and the clinical impact of targeted therapy with ALK inhibitors","volume":"6","author":"Chia","year":"2014","journal-title":"Clin. Epidemiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1200\/JCO.2011.35.6345","article-title":"ROS1 rearrangements define a unique molecular class of lung cancers","volume":"30","author":"Bergethon","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1002\/cncr.29042","article-title":"Clinicopathologic features and outcomes of patients with lung adenocarcinomas harboring BRAF mutations in the Lung Cancer Mutation Consortium","volume":"121","author":"Villaruz","year":"2015","journal-title":"Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1158\/2159-8290.CD-15-0285","article-title":"Activation of MET via diverse exon 14 splicing alterations occurs in multiple tumor types and confers clinical sensitivity to MET inhibitors","volume":"5","author":"Frampton","year":"2015","journal-title":"Cancer Discov."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1158\/2159-8290.CD-14-0765","article-title":"TRKing down an old oncogene in a new era of targeted therapy","volume":"5","author":"Vaishnavi","year":"2015","journal-title":"Cancer Discov."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/nrclinonc.2017.175","article-title":"Targeting RET-driven cancers: Lessons from evolving preclinical and clinical landscapes","volume":"15","author":"Drilon","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"101978","DOI":"10.1016\/j.ctrv.2020.101978","article-title":"KRAS as a druggable target in NSCLC: Rising like a phoenix after decades of development failures","volume":"85","author":"Friedlaender","year":"2020","journal-title":"Cancer Treat. Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.lungcan.2014.10.014","article-title":"HER2 gene mutations in non-small cell lung carcinomas: Concurrence with Her2 gene amplification and Her2 protein expression and phosphorylation","volume":"87","author":"Suzuki","year":"2015","journal-title":"Lung Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1158\/2159-8290.CD-17-1004","article-title":"Response to ERBB3-Directed Targeted Therapy in NRG1-Rearranged Cancers","volume":"8","author":"Drilon","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4966","DOI":"10.1158\/1078-0432.CCR-19-0160","article-title":"Detection of NRG1 Gene Fusions in Solid Tumors","volume":"25","author":"Jonna","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1007\/s10147-014-0760-9","article-title":"Frequency of brain metastases in non-small-cell lung cancer, and their association with epidermal growth factor receptor mutations","volume":"20","author":"Iuchi","year":"2015","journal-title":"Int. J. Clin. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.lungcan.2015.01.020","article-title":"Brain metastases in patients with EGFR-mutated or ALK-rearranged non-small-cell lung cancers","volume":"88","author":"Rangachari","year":"2015","journal-title":"Lung Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.lungcan.2014.01.006","article-title":"EGFR mutated non-small cell lung cancer patients: More prone to development of bone and brain metastases?","volume":"84","author":"Hendriks","year":"2014","journal-title":"Lung Cancer"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Remon, J., and Besse, B. (2018). Brain Metastases in Oncogene-Addicted Non-Small Cell Lung Cancer Patients: Incidence and Treatment. Front. Oncol., 8.","DOI":"10.3389\/fonc.2018.00088"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4502","DOI":"10.1002\/cncr.27409","article-title":"Oncogene status predicts patterns of metastatic spread in treatment-naive nonsmall cell lung cancer","volume":"118","author":"Doebele","year":"2012","journal-title":"Cancer"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1200\/JCO.2015.62.0138","article-title":"Extended Survival and Prognostic Factors for Patients with ALK-Rearranged Non-Small-Cell Lung Cancer and Brain Metastasis","volume":"34","author":"Johung","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2385","DOI":"10.1056\/NEJMoa1214886","article-title":"Crizotinib versus chemotherapy in advanced ALK-positive lung cancer","volume":"368","author":"Shaw","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1056\/NEJMoa1408440","article-title":"First-line crizotinib versus chemotherapy in ALK-positive lung cancer","volume":"371","author":"Solomon","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1200\/PO.17.00063","article-title":"Patterns of Metastatic Spread and Mechanisms of Resistance to Crizotinib in ROS1-Positive Non-Small-Cell Lung Cancer","volume":"2017","author":"Gainor","year":"2017","journal-title":"JCO Precis. Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4160","DOI":"10.1158\/1078-0432.CCR-21-0800","article-title":"Intracranial Efficacy of Selpercatinib in RET Fusion-Positive Non-Small Cell Lung Cancers on the LIBRETTO-001 Trial","volume":"27","author":"Subbiah","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"39721","DOI":"10.1038\/srep39721","article-title":"KRAS-mutation incidence and prognostic value are metastatic site-specific in lung adenocarcinoma: Poor prognosis in patients with KRAS mutation and bone metastasis","volume":"7","author":"Lohinai","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1007\/s10555-015-9592-y","article-title":"Insights into brain metastasis in patients with ALK+ lung cancer: Is the brain truly a sanctuary?","volume":"34","author":"Toyokawa","year":"2015","journal-title":"Cancer Metastasis Rev."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1016\/j.jtho.2018.07.001","article-title":"The Incidence of Brain Metastases in Stage IV ROS1-Rearranged Non-Small Cell Lung Cancer and Rate of Central Nervous System Progression on Crizotinib","volume":"13","author":"Patil","year":"2018","journal-title":"J. Thorac. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.lungcan.2019.05.011","article-title":"Impact of MET inhibitors on survival among patients with non-small cell lung cancer harboring MET exon 14 mutations: A retrospective analysis","volume":"133","author":"Awad","year":"2019","journal-title":"Lung Cancer"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4380","DOI":"10.1002\/cncr.32461","article-title":"Frequency and outcomes of brain metastases in patients with HER2-mutant lung cancers","volume":"125","author":"Offin","year":"2019","journal-title":"Cancer"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3290","DOI":"10.1200\/JCO.2018.78.3118","article-title":"CNS Response to Osimertinib Versus Standard Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Patients With Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer","volume":"36","author":"Reungwetwattana","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1200\/JCO.22.00393","article-title":"Selpercatinib in Patients With RET Fusion-Positive Non-Small-Cell Lung Cancer: Updated Safety and Efficacy From the Registrational LIBRETTO-001 Phase I\/II Trial","volume":"41","author":"Drilon","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2858","DOI":"10.1200\/JCO.2015.63.5888","article-title":"Intracranial Efficacy of Crizotinib Versus Chemotherapy in Patients With Advanced ALK-Positive Non-Small-Cell Lung Cancer: Results From PROFILE 1014","volume":"34","author":"Solomon","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2027","DOI":"10.1056\/NEJMoa1810171","article-title":"Brigatinib versus Crizotinib in ALK-Positive Non-Small-Cell Lung Cancer","volume":"379","author":"Camidge","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2214","DOI":"10.1093\/annonc\/mdy405","article-title":"Alectinib versus crizotinib in treatment-naive anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer: CNS efficacy results from the ALEX study","volume":"29","author":"Gadgeel","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1016\/j.jtho.2019.03.007","article-title":"Updated Efficacy and Safety Data and Impact of the EML4-ALK Fusion Variant on the Efficacy of Alectinib in Untreated ALK-Positive Advanced Non-Small Cell Lung Cancer in the Global Phase III ALEX Study","volume":"14","author":"Camidge","year":"2019","journal-title":"J. Thorac. Oncol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1056\/NEJMoa2027187","article-title":"First-Line Lorlatinib or Crizotinib in Advanced ALK-Positive Lung Cancer","volume":"383","author":"Shaw","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1016\/S1470-2045(19)30655-2","article-title":"Lorlatinib in advanced ROS1-positive non-small-cell lung cancer: A multicentre, open-label, single-arm, phase 1-2 trial","volume":"20","author":"Shaw","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1200\/JCO.20.03025","article-title":"Updated Integrated Analysis of the Efficacy and Safety of Entrectinib in Locally Advanced or Metastatic ROS1 Fusion-Positive Non-Small-Cell Lung Cancer","volume":"39","author":"Dziadziuszko","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"v162","DOI":"10.1093\/annonc\/mdz244.006","article-title":"Safety and preliminary clinical activity of repotrectinib in patients with advanced ROS1\/TRK fusion-positive solid tumors (TRIDENT-1 study)","volume":"30","author":"Drilon","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"S1123","DOI":"10.1016\/j.jtho.2021.08.547","article-title":"Efficacy of Sotorasib in KRAS p.G12C-Mutated NSCLC with Stable Brain Metastases: A Post-Hoc Analysis of CodeBreaK 100","volume":"16","author":"Ramalingam","year":"2021","journal-title":"J. Thorac. Oncol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"4472","DOI":"10.1200\/JCO.23.00046","article-title":"Intracranial Efficacy of Adagrasib in Patients From the KRYSTAL-1 Trial With KRAS(G12C)-Mutated Non-Small-Cell Lung Cancer Who Have Untreated CNS Metastases","volume":"41","author":"Negrao","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1056\/NEJMoa2002787","article-title":"Capmatinib in MET Exon 14-Mutated or MET-Amplified Non-Small-Cell Lung Cancer","volume":"383","author":"Wolf","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"9084","DOI":"10.1200\/JCO.2021.39.15_suppl.9084","article-title":"Intracranial activity of tepotinib in patients (pts) with MET exon 14 (METex14) skipping NSCLC enrolled in VISION","volume":"39","author":"Patel","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"9093","DOI":"10.1200\/JCO.2021.39.15_suppl.9093","article-title":"CNS activity of poziotinib in NSCLC with exon 20 insertion mutations","volume":"39","author":"Le","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1007\/s00280-014-2578-6","article-title":"Antitumor activity of the selective ALK inhibitor alectinib in models of intracranial metastases","volume":"74","author":"Kodama","year":"2014","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"5130","DOI":"10.1158\/1078-0432.CCR-16-0399","article-title":"Preclinical Comparison of Osimertinib with Other EGFR-TKIs in EGFR-Mutant NSCLC Brain Metastases Models, and Early Evidence of Clinical Brain Metastases Activity","volume":"22","author":"Ballard","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.lungcan.2018.04.015","article-title":"Analysis of central nervous system efficacy in the J-ALEX study of alectinib versus crizotinib in ALK-positive non-small-cell lung cancer","volume":"121","author":"Nishio","year":"2018","journal-title":"Lung Cancer"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"418","DOI":"10.20892\/j.issn.2095-3941.2017.0079","article-title":"Brain metastasis in non-small cell lung cancer (NSCLC) patients with uncommon EGFR mutations: A report of seven cases and literature review","volume":"14","author":"Er","year":"2017","journal-title":"Cancer Biol. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"75712","DOI":"10.18632\/oncotarget.20095","article-title":"EGFR TKI as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer","volume":"8","author":"Nan","year":"2017","journal-title":"Oncotarget"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2866","DOI":"10.1200\/JCO.2010.33.4235","article-title":"Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin\/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS)","volume":"29","author":"Fukuoka","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1200\/JCO.2011.36.8456","article-title":"First-SIGNAL: First-line single-agent iressa versus gemcitabine and cisplatin trial in never-smokers with adenocarcinoma of the lung","volume":"30","author":"Han","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1093\/annonc\/mds214","article-title":"Updated overall survival results from a randomized phase III trial comparing gefitinib with carboplatin-paclitaxel for chemo-naive non-small cell lung cancer with sensitive EGFR gene mutations (NEJ002)","volume":"24","author":"Inoue","year":"2013","journal-title":"Ann. Oncol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S1470-2045(09)70364-X","article-title":"Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): An open label, randomised phase 3 trial","volume":"11","author":"Mitsudomi","year":"2010","journal-title":"Lancet Oncol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S1470-2045(11)70393-X","article-title":"Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): A multicentre, open-label, randomised phase 3 trial","volume":"13","author":"Rosell","year":"2012","journal-title":"Lancet Oncol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/S1470-2045(11)70184-X","article-title":"Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): A multicentre, open-label, randomised, phase 3 study","volume":"12","author":"Zhou","year":"2011","journal-title":"Lancet Oncol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3327","DOI":"10.1200\/JCO.2012.44.2806","article-title":"Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations","volume":"31","author":"Sequist","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/S1470-2045(13)70604-1","article-title":"Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): An open-label, randomised phase 3 trial","volume":"15","author":"Wu","year":"2014","journal-title":"Lancet Oncol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/S1470-2045(14)71173-8","article-title":"Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): Analysis of overall survival data from two randomised, phase 3 trials","volume":"16","author":"Yang","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"3337","DOI":"10.1200\/JCO.2011.40.9433","article-title":"Randomized phase II study of dacomitinib (PF-00299804), an irreversible pan-human epidermal growth factor receptor inhibitor, versus erlotinib in patients with advanced non-small-cell lung cancer","volume":"30","author":"Ramalingam","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1158\/1078-0432.CCR-10-2277","article-title":"Rebiopsy of lung cancer patients with acquired resistance to EGFR inhibitors and enhanced detection of the T790M mutation using a locked nucleic acid-based assay","volume":"17","author":"Arcila","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"75ra26","DOI":"10.1126\/scitranslmed.3002003","article-title":"Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors","volume":"3","author":"Sequist","year":"2011","journal-title":"Sci. Transl. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2240","DOI":"10.1158\/1078-0432.CCR-12-2246","article-title":"Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers","volume":"19","author":"Yu","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1056\/NEJMoa1612674","article-title":"Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer","volume":"376","author":"Mok","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2296","DOI":"10.1056\/NEJMc1602688","article-title":"Update to Rociletinib Data with the RECIST Confirmed Response Rate","volume":"374","author":"Sequist","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1002\/cncr.33385","article-title":"Olmutinib in T790M-positive non-small cell lung cancer after failure of first-line epidermal growth factor receptor-tyrosine kinase inhibitor therapy: A global, phase 2 study","volume":"127","author":"Park","year":"2021","journal-title":"Cancer"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1200\/JCO.2017.74.7576","article-title":"Osimertinib As First-Line Treatment of EGFR Mutation-Positive Advanced Non-Small-Cell Lung Cancer","volume":"36","author":"Ramalingam","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1056\/NEJMoa1413654","article-title":"Rociletinib in EGFR-mutated non-small-cell lung cancer","volume":"372","author":"Sequist","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1016\/j.jtho.2018.03.025","article-title":"First-in-Human Phase I Study of AC0010, a Mutant-Selective EGFR Inhibitor in Non-Small Cell Lung Cancer: Safety, Efficacy, and Potential Mechanism of Resistance","volume":"13","author":"Ma","year":"2018","journal-title":"J. Thorac. Oncol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.canlet.2016.11.008","article-title":"EAI045: The fourth-generation EGFR inhibitor overcoming T790M and C797S resistance","volume":"385","author":"Wang","year":"2017","journal-title":"Cancer Lett."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s13045-016-0290-1","article-title":"EGFR C797S mutation mediates resistance to third-generation inhibitors in T790M-positive non-small cell lung cancer","volume":"9","author":"Wang","year":"2016","journal-title":"J. Hematol. Oncol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/nature17960","article-title":"Overcoming EGFR(T790M) and EGFR(C797S) resistance with mutant-selective allosteric inhibitors","volume":"534","author":"Jia","year":"2016","journal-title":"Nature"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1007\/s43440-020-00131-0","article-title":"Advances in targeting EGFR allosteric site as anti-NSCLC therapy to overcome the drug resistance","volume":"72","author":"Maity","year":"2020","journal-title":"Pharmacol. Rep."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2288","DOI":"10.1158\/1535-7163.MCT-20-0229","article-title":"CH7233163 Overcomes Osimertinib-Resistant EGFR-Del19\/T790M\/C797S Mutation","volume":"19","author":"Kashima","year":"2020","journal-title":"Mol. Cancer Ther."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1158\/2159-8290.CD-18-0903","article-title":"Single and Dual Targeting of Mutant EGFR with an Allosteric Inhibitor","volume":"9","author":"To","year":"2019","journal-title":"Cancer Discov."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Kelly, W.J., Shah, N.J., and Subramaniam, D.S. (2018). Management of Brain Metastases in Epidermal Growth Factor Receptor Mutant Non-Small-Cell Lung Cancer. Front. Oncol., 8.","DOI":"10.3389\/fonc.2018.00208"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1016\/S1470-2045(16)30562-9","article-title":"Cabozantinib in patients with advanced RET-rearranged non-small-cell lung cancer: An open-label, single-centre, phase 2, single-arm trial","volume":"17","author":"Drilon","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1016\/j.jtho.2018.07.004","article-title":"Frequency of Brain Metastases and Multikinase Inhibitor Outcomes in Patients With RET-Rearranged Lung Cancers","volume":"13","author":"Drilon","year":"2018","journal-title":"J. Thorac. Oncol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/S1470-2045(21)00247-3","article-title":"Pralsetinib for RET fusion-positive non-small-cell lung cancer (ARROW): A multi-cohort, open-label, phase 1\/2 study","volume":"22","author":"Gainor","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_109","first-page":"PO.19.00021","article-title":"Response to Selective RET Inhibition With LOXO-292 in a Patient With RET Fusion-Positive Lung Cancer With Leptomeningeal Metastases","volume":"3","author":"Guo","year":"2019","journal-title":"JCO Precis. Oncol."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Jablonska, P.A., Bosch-Barrera, J., Serrano, D., Valiente, M., Calvo, A., and Aristu, J. (2021). Challenges and Novel Opportunities of Radiation Therapy for Brain Metastases in Non-Small Cell Lung Cancer. Cancers, 13.","DOI":"10.3390\/cancers13092141"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.ctrv.2015.03.009","article-title":"Beyond EGFR and ALK inhibition: Unravelling and exploiting novel genetic alterations in advanced non small-cell lung cancer","volume":"41","author":"Califano","year":"2015","journal-title":"Cancer Treat. Rev."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1056\/NEJMoa1406766","article-title":"Crizotinib in ROS1-rearranged non-small-cell lung cancer","volume":"371","author":"Shaw","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1093\/annonc\/mdz131","article-title":"Crizotinib in ROS1-rearranged advanced non-small-cell lung cancer (NSCLC): Updated results, including overall survival, from PROFILE 1001","volume":"30","author":"Shaw","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1056\/NEJMoa1704795","article-title":"Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer","volume":"377","author":"Peters","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0140-6736(17)30565-2","article-title":"Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): An open-label, randomised phase 3 trial","volume":"390","author":"Hida","year":"2017","journal-title":"Lancet"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/S0140-6736(17)30123-X","article-title":"First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): A randomised, open-label, phase 3 study","volume":"389","author":"Soria","year":"2017","journal-title":"Lancet"},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Zou, Z., Xing, P., Hao, X., Wang, Y., Song, X., Shan, L., Zhang, C., Liu, Z., Ma, K., and Dong, G. (2022). Intracranial efficacy of alectinib in ALK-positive NSCLC patients with CNS metastases-a multicenter retrospective study. BMC Med., 20.","DOI":"10.1186\/s12916-021-02207-x"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1016\/S1470-2045(17)30680-0","article-title":"Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: An international, multicentre, open-label, single-arm first-in-man phase 1 trial","volume":"18","author":"Shaw","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"S298","DOI":"10.21037\/tlcr.2019.05.15","article-title":"Brain metastases in oncogene-driven non-small cell lung cancer","volume":"8","author":"Nishino","year":"2019","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1158\/2159-8290.CD-16-0596","article-title":"Molecular Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in ALK-Rearranged Lung Cancer","volume":"6","author":"Gainor","year":"2016","journal-title":"Cancer Discov."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Petrelli, F., Lazzari, C., Ardito, R., Borgonovo, K., Bulotta, A., Conti, B., Cabiddu, M., Capitanio, J.F., Brighenti, M., and Ghilardi, M. (2018). Efficacy of ALK inhibitors on NSCLC brain metastases: A systematic review and pooled analysis of 21 studies. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0201425"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1358\/dot.2019.55.10.3030646","article-title":"Targeted therapies for ROS1-rearranged non-small cell lung cancer","volume":"55","author":"Patil","year":"2019","journal-title":"Drugs Today"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.lungcan.2019.02.025","article-title":"CNS metastasis in ROS1+ NSCLC: An urgent call to action, to understand, and to overcome","volume":"130","author":"Ou","year":"2019","journal-title":"Lung Cancer"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/S0959-8049(22)00812-7","article-title":"Pivotal topline data from the phase 1\/2 TRIDENT-1 trial of repotrectinib in patients with ROS1+ advanced non-small cell lung cancer (NSCLC)","volume":"174","author":"Cho","year":"2022","journal-title":"Eur. J. Cancer"},{"key":"ref_125","first-page":"100108","article-title":"Efficacy of Taletrectinib (AB-106\/DS-6051b) in ROS1+ NSCLC: An Updated Pooled Analysis of U.S. and Japan Phase 1 Studies","volume":"2","author":"Ou","year":"2021","journal-title":"JTO Clin. Res. Rep."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Cascetta, P., Marinello, A., Lazzari, C., Gregorc, V., Planchard, D., Bianco, R., Normanno, N., and Morabito, A. (2022). KRAS in NSCLC: State of the Art and Future Perspectives. Cancers, 14.","DOI":"10.3390\/cancers14215430"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1159\/000525341","article-title":"Sotorasib Shows Intracranial Activity in Patients with KRAS G12C-Mutated Adenocarcinoma of the Lung and Untreated Active Brain Metastases","volume":"15","author":"Koster","year":"2022","journal-title":"Case Rep. Oncol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1056\/NEJMoa2004407","article-title":"Tepotinib in Non-Small-Cell Lung Cancer with MET Exon 14 Skipping Mutations","volume":"383","author":"Paik","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s40291-021-00568-w","article-title":"MET-Targeted Therapies and Clinical Outcomes: A Systematic Literature Review","volume":"26","author":"Dong","year":"2022","journal-title":"Mol. Diagn. Ther."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1080\/14656566.2020.1798930","article-title":"Treating non-small cell lung cancer with selumetinib: An up-to-date drug evaluation","volume":"21","author":"Imyanitov","year":"2020","journal-title":"Expert. Opin. Pharmacother."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1080\/13543784.2017.1351543","article-title":"Selumetinib for the treatment of non-small cell lung cancer","volume":"26","author":"Casaluce","year":"2017","journal-title":"Expert. Opin. Investig. Drugs"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1097\/JTO.0000000000000625","article-title":"Targeted Therapy for Patients with BRAF-Mutant Lung Cancer: Results from the European EURAF Cohort","volume":"10","author":"Gautschi","year":"2015","journal-title":"J. Thorac. Oncol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.lungcan.2014.05.009","article-title":"BRAF V600E-mutated lung adenocarcinoma with metastases to the brain responding to treatment with vemurafenib","volume":"85","author":"Robinson","year":"2014","journal-title":"Lung Cancer"},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Sforza, V., Palumbo, G., Cascetta, P., Carillio, G., Manzo, A., Montanino, A., Sandomenico, C., Costanzo, R., Esposito, G., and Laudato, F. (2022). BRAF Inhibitors in Non-Small Cell Lung Cancer. Cancers, 14.","DOI":"10.3390\/cancers14194863"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.jtho.2021.08.011","article-title":"Phase 2 Study of Dabrafenib Plus Trametinib in Patients With BRAF V600E-Mutant Metastatic NSCLC: Updated 5-Year Survival Rates and Genomic Analysis","volume":"17","author":"Planchard","year":"2022","journal-title":"J. Thorac. Oncol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/S1470-2045(16)00077-2","article-title":"Dabrafenib in patients with BRAF(V600E)-positive advanced non-small-cell lung cancer: A single-arm, multicentre, open-label, phase 2 trial","volume":"17","author":"Planchard","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/S1470-2045(17)30429-1","article-title":"Dabrafenib plus trametinib in patients with BRAF(V600)-mutant melanoma brain metastases (COMBI-MB): A multicentre, multicohort, open-label, phase 2 trial","volume":"18","author":"Davies","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S1470-2045(21)00578-7","article-title":"Dabrafenib plus trametinib in patients with BRAF(V600E)-mutant low-grade and high-grade glioma (ROAR): A multicentre, open-label, single-arm, phase 2, basket trial","volume":"23","author":"Wen","year":"2022","journal-title":"Lancet Oncol."},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Liu, F., Wei, Y., Zhang, H., Jiang, J., Zhang, P., and Chu, Q. (2022). NTRK Fusion in Non-Small Cell Lung Cancer: Diagnosis, Therapy, and TRK Inhibitor Resistance. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.864666"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1093\/annonc\/mdy539","article-title":"Larotrectinib in adult patients with solid tumours: A multi-centre, open-label, phase I dose-escalation study","volume":"30","author":"Hong","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/S1470-2045(18)30119-0","article-title":"Larotrectinib for paediatric solid tumours harbouring NTRK gene fusions: Phase 1 results from a multicentre, open-label, phase 1\/2 study","volume":"19","author":"Laetsch","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1056\/NEJMoa1714448","article-title":"Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children","volume":"378","author":"Drilon","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/S1470-2045(19)30856-3","article-title":"Larotrectinib in patients with TRK fusion-positive solid tumours: A pooled analysis of three phase 1\/2 clinical trials","volume":"21","author":"Hong","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S1470-2045(19)30691-6","article-title":"Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: Integrated analysis of three phase 1-2 trials","volume":"21","author":"Doebele","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"100260","DOI":"10.1016\/j.esmoop.2021.100260","article-title":"Targeting HER2 in non-small-cell lung cancer (NSCLC): A glimpse of hope? An updated review on therapeutic strategies in NSCLC harbouring HER2 alterations","volume":"6","author":"Riudavets","year":"2021","journal-title":"ESMO Open"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1093\/annonc\/mdv186","article-title":"Targeting HER2 aberrations as actionable drivers in lung cancers: Phase II trial of the pan-HER tyrosine kinase inhibitor dacomitinib in patients with HER2-mutant or amplified tumors","volume":"26","author":"Kris","year":"2015","journal-title":"Ann. Oncol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/j.jtho.2023.03.016","article-title":"Poziotinib in Treatment-Naive NSCLC Harboring HER2 Exon 20 Mutations: ZENITH20-4, A Multicenter, Multicohort, Open-Label, Phase 2 Trial (Cohort 4)","volume":"18","author":"Cornelissen","year":"2023","journal-title":"J. Thorac. Oncol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1200\/JCO.21.01323","article-title":"Poziotinib in Non-Small-Cell Lung Cancer Harboring HER2 Exon 20 Insertion Mutations After Prior Therapies: ZENITH20-2 Trial","volume":"40","author":"Le","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1056\/NEJMoa2112431","article-title":"Trastuzumab Deruxtecan in HER2-Mutant Non-Small-Cell Lung Cancer","volume":"386","author":"Li","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1158\/2159-8290.CD-19-1014","article-title":"Targeting HER2 with Trastuzumab Deruxtecan: A Dose-Expansion, Phase I Study in Multiple Advanced Solid Tumors","volume":"10","author":"Tsurutani","year":"2020","journal-title":"Cancer Discov."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"9504","DOI":"10.1200\/JCO.2020.38.15_suppl.9504","article-title":"Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2-mutated metastatic non-small cell lung cancer (NSCLC): Interim results of DESTINY-Lung01","volume":"38","author":"Smit","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"5459","DOI":"10.18632\/oncotarget.23616","article-title":"Targeted drugs for systemic therapy of lung cancer with brain metastases","volume":"9","author":"Sun","year":"2018","journal-title":"Oncotarget"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1056\/NEJMoa1713137","article-title":"Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer","volume":"378","author":"Soria","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1016\/j.jtho.2021.07.035","article-title":"Brigatinib Versus Crizotinib in ALK Inhibitor-Naive Advanced ALK-Positive NSCLC: Final Results of Phase 3 ALTA-1L Trial","volume":"16","author":"Camidge","year":"2021","journal-title":"J. Thorac. Oncol."},{"key":"ref_155","first-page":"100332","article-title":"Long-Term Efficacy and Safety of Entrectinib in ROS1 Fusion-Positive NSCLC","volume":"3","author":"Drilon","year":"2022","journal-title":"JTO Clin. Res. Rep."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1056\/NEJMoa2302299","article-title":"Repotrectinib in ROS1 Fusion-Positive Non-Small-Cell Lung Cancer","volume":"390","author":"Drilon","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"2371","DOI":"10.1056\/NEJMoa2103695","article-title":"Sotorasib for Lung Cancers with KRAS p","volume":"384","author":"Skoulidis","year":"2021","journal-title":"G12C Mutation. N. Engl. J. Med."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1158\/1078-0432.CCR-19-1871","article-title":"Preclinical Comparison of the Blood-brain barrier Permeability of Osimertinib with Other EGFR TKIs","volume":"27","author":"Colclough","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.ccell.2020.03.007","article-title":"Intratumor Heterogeneity: The Rosetta Stone of Therapy Resistance","volume":"37","author":"Marusyk","year":"2020","journal-title":"Cancer Cell"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"102545","DOI":"10.1016\/j.ctrv.2023.102545","article-title":"Immunotherapy-based combinations in metastatic NSCLC","volume":"116","author":"Desai","year":"2023","journal-title":"Cancer Treat. Rev."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/13\/6961\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:04:27Z","timestamp":1760108667000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/13\/6961"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,26]]},"references-count":160,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["ijms25136961"],"URL":"https:\/\/doi.org\/10.3390\/ijms25136961","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,26]]}}}