{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T03:37:46Z","timestamp":1792899466392,"version":"4.5.0"},"reference-count":30,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"4","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Cetuximab plus paclitaxel (CET + PTX) is frequently administered after immune checkpoint inhibitor (ICI) therapy in patients with recurrent or metastatic head and neck squamous cell carcinoma (R\/M-HNSCC). However, the relation between responses to these two treatment lines has remained unclear. We aimed to clarify this relation and its potential mechanisms, focusing on the patients treated with pembrolizumab plus chemotherapy and subsequent CET + PTX.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PATIENTS AND METHODS<\/jats:title>\n                    <jats:p>We retrospectively reviewed patients with R\/M-HNSCC who received pembrolizumab plus chemotherapy and subsequent CET + PTX at Tohoku University Hospital between April 2020 and November 2025. Clinical outcomes of CET + PTX were assessed according to response to prior pembrolizumab plus chemotherapy. Gene expression and immunohistochemical (IHC) analyses of pretreatment tumor samples, as well as HNSCC cell\u2013based assays, were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      This study included 30 patients. The overall response rate (ORR) to subsequent CET + PTX was 57%. The ORR and progression-free survival (PFS) of CET + PTX were significantly greater in patients who showed progressive disease on pembrolizumab plus chemotherapy than in responders (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .01). Gene expression analyses revealed enrichment of Janus kinase (JAK)\u2013STAT signaling pathways in pembrolizumab plus chemotherapy nonresponders who responded to CET + PTX. Consistently, high tumor expression of phosphorylated STAT3 was observed exclusively in this subgroup by IHC. CET sensitivity across HNSCC cell lines correlated with STAT3 phosphorylation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Responses to pembrolizumab plus chemotherapy and subsequent CET + PTX were inversely associated in R\/M-HNSCC. Activation of the JAK-STAT signaling pathway, particularly STAT3 phosphorylation, may identify tumors resistant to pembrolizumab plus chemotherapy but sensitive to CET + PTX, thereby guiding post-ICI treatment selection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/po-25-01050","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T19:59:11Z","timestamp":1776974351000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Inverse Relation Between Responses to Pembrolizumab Plus Chemotherapy and Subsequent Cetuximab Plus Paclitaxel in Head and Neck Cancer: Role of the Janus Kinase\u2013Signal Transducer and Activator of Transcription Signaling Pathway"],"prefix":"10.1200","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0179-3789","authenticated-orcid":true,"given":"Ken","family":"Saijo","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Tohoku University Hospital, Sendai, Japan"},{"name":"Department of Clinical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroo","family":"Imai","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Tohoku University Hospital, Sendai, Japan"},{"name":"Department of Clinical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Iwasaki","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Tohoku University Hospital, Sendai, Japan"},{"name":"Department of Clinical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5946-8626","authenticated-orcid":true,"given":"Ryo","family":"Ishii","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenjiro","family":"Higashi","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0652-7041","authenticated-orcid":true,"given":"Akira","family":"Ohkoshi","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9976-2632","authenticated-orcid":true,"given":"Yuto","family":"Yamazaki","sequence":"additional","affiliation":[{"name":"Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoaki","family":"Shirakawa","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Tohoku University Hospital, Sendai, Japan"},{"name":"Department of Clinical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Tohoku University Hospital, Sendai, Japan"},{"name":"Department of Clinical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4482-6210","authenticated-orcid":true,"given":"Shonosuke","family":"Wakayama","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Tohoku University Hospital, Sendai, Japan"},{"name":"Department of Clinical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryunosuke","family":"Numakura","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Tohoku University Hospital, Sendai, Japan"},{"name":"Department of Clinical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8560-9760","authenticated-orcid":true,"given":"Yuya","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Tohoku University Hospital, Sendai, Japan"},{"name":"Department of Clinical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakura","family":"Taniguchi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Tohoku University Hospital, Sendai, Japan"},{"name":"Department of Clinical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Kasahara","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Tohoku University Hospital, Sendai, Japan"},{"name":"Department of Clinical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5572-1337","authenticated-orcid":true,"given":"Kota","family":"Ouchi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Tohoku University Hospital, Sendai, Japan"},{"name":"Department of Clinical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2502-3666","authenticated-orcid":true,"given":"Keigo","family":"Komine","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Tohoku University Hospital, Sendai, Japan"},{"name":"Department of Clinical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidekazu","family":"Shirota","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Tohoku University Hospital, Sendai, Japan"},{"name":"Department of Clinical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9306-7041","authenticated-orcid":true,"given":"Masanobu","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Tohoku University Hospital, Sendai, Japan"},{"name":"Department of Clinical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0195-815X","authenticated-orcid":true,"given":"Takashi","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukio","family":"Katori","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3023-1227","authenticated-orcid":true,"given":"Chikashi","family":"Ishioka","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Tohoku University Hospital, Sendai, Japan"},{"name":"Department of Clinical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3280-4850","authenticated-orcid":true,"given":"Hisato","family":"Kawakami","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Tohoku University Hospital, Sendai, Japan"},{"name":"Department of Clinical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_8_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2025.102910"},{"key":"e_1_3_8_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-018-0202-2"},{"key":"e_1_3_8_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2015.11.019"},{"key":"e_1_3_8_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1445"},{"key":"e_1_3_8_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0802656"},{"key":"e_1_3_8_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1602252"},{"key":"e_1_3_8_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31999-8"},{"key":"e_1_3_8_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32591-7"},{"key":"e_1_3_8_10_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1230731"},{"key":"e_1_3_8_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12672-025-02256-1"},{"key":"e_1_3_8_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2024.103476"},{"key":"e_1_3_8_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1221352"},{"key":"e_1_3_8_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2019.08.026"},{"key":"e_1_3_8_15_2","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-003026"},{"key":"e_1_3_8_16_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16234056"},{"key":"e_1_3_8_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-79130-7"},{"key":"e_1_3_8_18_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI91190"},{"key":"e_1_3_8_19_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-018-2486-6"},{"key":"e_1_3_8_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.2409"},{"key":"e_1_3_8_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.21475"},{"key":"e_1_3_8_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3835(03)00345-8"},{"key":"e_1_3_8_23_2","first-page":"1","article-title":"Amphiregulin promotes vascular endothelial growth Factor-C expression and lymphangiogenesis through STAT3 activation in human chondrosarcoma cells","volume":"52","author":"Huang YW","year":"2019","unstructured":"Huang YW, Tsai HC, Wang SW, et al: Amphiregulin promotes vascular endothelial growth Factor-C expression and lymphangiogenesis through STAT3 activation in human chondrosarcoma cells. Cell Physiol Biochem 52:1-15, 2019","journal-title":"Cell Physiol Biochem"},{"key":"e_1_3_8_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/cas.13332"},{"key":"e_1_3_8_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.ade8520"},{"key":"e_1_3_8_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2022.100878"},{"key":"e_1_3_8_27_2","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.20846"},{"key":"e_1_3_8_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(21)00136-4"},{"key":"e_1_3_8_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/hed.27344"},{"key":"e_1_3_8_30_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-023-02691-4"},{"key":"e_1_3_8_31_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2415434"}],"container-title":["JCO Precision Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/PO-25-01050","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T19:59:12Z","timestamp":1776974352000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/PO-25-01050"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":30,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1200\/PO-25-01050"],"URL":"https:\/\/doi.org\/10.1200\/po-25-01050","relation":{},"ISSN":["2473-4284"],"issn-type":[{"value":"2473-4284","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"2025-10-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-02","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2501050"}}