{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T17:25:05Z","timestamp":1793381105428,"version":"4.5.0"},"reference-count":15,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,12,27]],"date-time":"2024-12-27T00:00:00Z","timestamp":1735257600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Thoracic Cancer"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Concurrent mutations in tumor protein p53 (TP53) or Kelch\u2010like ECH\u2010associated protein 1\u2010nuclear factor erythroid 2\u2010related factor 2\u2010pathway components are linked to poor outcomes in <jats:italic>epidermal growth factor receptor (EGFR<\/jats:italic>)\u2010mutant non\u2010small cell lung cancer (NSCLC), but the impact of triple mutations remains unclear. We report a case of <jats:italic>EGFR<\/jats:italic>\u2010, <jats:italic>TP53<\/jats:italic>\u2010, and <jats:italic>Cullin 3<\/jats:italic> (<jats:italic>CUL3<\/jats:italic>)\u2010mutant NSCLC in a 43\u2010year\u2010old woman with widespread metastases at diagnosis, including those in the contralateral lung, distant lymph nodes, pericardium, liver, bones, left adrenal gland, and brain. She received osimertinib as first\u2010line therapy, but pericardial effusion and liver metastases progressed rapidly over 3 months, and she was switched to carboplatin and pemetrexed. By the eighth cycle of pemetrexed, the bone metastases had progressed, resulting in disseminated intravascular coagulation (DIC) due to bone marrow carcinomatosis. The patient received third\u2010line therapy with albumin\u2010bound paclitaxel and fourth\u2010line therapy with docetaxel, but further treatment was suspended owing to DIC progression. She passed away 23\u2009months after the initiation of osimertinib. Public database analysis revealed that the <jats:italic>EGFR<\/jats:italic>\/<jats:italic>TP53<\/jats:italic>\/<jats:italic>CUL3<\/jats:italic> triple mutation accounts for 0.4% of <jats:italic>EGFR<\/jats:italic>\u2010mutant NSCLC cases, yielding significantly shorter survival than <jats:italic>EGFR<\/jats:italic> mutations alone and likely shorter than <jats:italic>EGFR<\/jats:italic>\/<jats:italic>TP53<\/jats:italic> double mutations. Gaining a deeper understanding of the clinical significance of coexisting genetic mutations in patients with <jats:italic>EGFR<\/jats:italic>\u2010mutant NSCLC will be crucial to develop future therapies.<\/jats:p>","DOI":"10.1111\/1759-7714.15523","type":"journal-article","created":{"date-parts":[[2024,12,27]],"date-time":"2024-12-27T11:49:00Z","timestamp":1735300140000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["<scp><i>EGFR<\/i><\/scp>, <scp><i>TP53<\/i><\/scp>, and <scp><i>CUL3<\/i><\/scp> Triple Mutation in Non\u2010Small Cell Lung Cancer and its Potentially Poor Prognosis: A Case Report and Database Analysis"],"prefix":"10.1111","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5434-5459","authenticated-orcid":false,"given":"Hiroto","family":"Hatano","sequence":"first","affiliation":[{"name":"Department of Thoracic Oncology National Cancer Center Hospital  Tokyo Japan"},{"name":"Department of Respiratory Medicine National Center for Global Health and Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4896-5824","authenticated-orcid":false,"given":"Tatsuya","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Thoracic Oncology National Cancer Center Hospital  Tokyo Japan"},{"name":"Department of Experimental Therapeutics National Cancer Center Hospital  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoko","family":"Higashiyama","sequence":"additional","affiliation":[{"name":"Department of Thoracic Oncology National Cancer Center Hospital  Tokyo Japan"},{"name":"Department of Experimental Therapeutics National Cancer Center Hospital  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Torasawa","sequence":"additional","affiliation":[{"name":"Department of Thoracic Oncology National Cancer Center Hospital  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Uehara","sequence":"additional","affiliation":[{"name":"Department of Thoracic Oncology National Cancer Center Hospital  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichiro","family":"Ohe","sequence":"additional","affiliation":[{"name":"Department of Thoracic Oncology National Cancer Center Hospital  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,27]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmorw.2024.100058"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.2147\/CMAR.S201513"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2019.05.002"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-17-0151"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-019-0179-8"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-14-1236"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology11091325"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.21037\/tlcr-21-754"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102726"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-5003"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-20-1385"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-47606-9"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1184079"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-24-0249"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2024.05.541"}],"container-title":["Thoracic Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1759-7714.15523","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T05:50:35Z","timestamp":1739512235000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1759-7714.15523"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,27]]},"references-count":15,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1111\/1759-7714.15523"],"URL":"https:\/\/doi.org\/10.1111\/1759-7714.15523","archive":["Portico"],"relation":{},"ISSN":["1759-7706","1759-7714"],"issn-type":[{"value":"1759-7706","type":"print"},{"value":"1759-7714","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,27]]},"assertion":[{"value":"2024-11-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e15523"}}