Youjun Deng, Yan Huang, Songhua Cai, Chujian Huang, Wenyi Liu, Ran Jia, Zhilin Sui, Heng Zou, Zhentao Yu, Xiaotong Guo
{"title":"Pembrolizumab治疗smarca4缺陷非小细胞肺癌:高肿瘤突变负担和程序性死亡-配体1(+)在循环肿瘤细胞上的表达,用于实时监测:一例报告","authors":"Youjun Deng, Yan Huang, Songhua Cai, Chujian Huang, Wenyi Liu, Ran Jia, Zhilin Sui, Heng Zou, Zhentao Yu, Xiaotong Guo","doi":"10.1097/CAD.0000000000001758","DOIUrl":null,"url":null,"abstract":"<p><p>Nonsmall cell lung cancer (NSCLC) with SMARCA4 deficiency represents a rare subset of lung tumors characterized by early metastasis, poor response to chemotherapy, and unfavorable prognosis. Established therapy strategies for SMARCA4-deficient NSCLC remain elusive. While immune checkpoint inhibitors have been proposed as a potential solution, their efficacy remains uncertain. Clinical factors such as tumor mutational burden (TMB), microsatellite instability, comutations, and programmed death-ligand 1 (PD-L1) expression may influence the treatment response of SMARCA4-deficient NSCLC. Additionally, PD-L1 expression on circulating tumor cells (CTCs) provides novel insights for monitoring, and its utility in SMARCA4-deficient NSCLC remains unexplored. The present report describes the case of a 71-year-old man diagnosed with SMARCA4-deficient NSCLC who had a history of heavy smoking and chronic cough. Imaging examination revealed metastatic lymph nodes. All serum tumor markers were elevated above the normal range. Histopathological and immunohistochemical analyses of the biopsy specimen from a primary lesion in the right upper lung demonstrated irregularly arranged tumor cells, SMARCA4 deficiency, and positive PD-L1 expression. Further next-generation sequencing confirmed SMARCA4 mutation, high TMB, and microsatellite stability (MSS). The patient received pembrolizumab treatment and experienced a sustained benefit for >40 months, with persistent PD-L1 expression on CTCs observed throughout the treatment. It was revealed that pembrolizumab therapy shows promise for patients with SMARCA4-deficient NSCLC with positive PD-L1 expression, high TMB, and MSS. Dynamic monitoring of PD-L1 status on CTCs may facilitate the assessment of the immunotherapy response, and the sustained positive PD-L1 expression on CTCs may imply continued benefit from immunotherapy for patients with SMARCA4-deficient NSCLC.</p>","PeriodicalId":7969,"journal":{"name":"Anti-Cancer Drugs","volume":" ","pages":""},"PeriodicalIF":2.2000,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Pembrolizumab treatment in SMARCA4-deficient nonsmall cell lung cancer: high tumor mutational burden and programmed death-ligand 1(+) expression on circulating tumor cells for real-time monitoring: a case report.\",\"authors\":\"Youjun Deng, Yan Huang, Songhua Cai, Chujian Huang, Wenyi Liu, Ran Jia, Zhilin Sui, Heng Zou, Zhentao Yu, Xiaotong Guo\",\"doi\":\"10.1097/CAD.0000000000001758\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Nonsmall cell lung cancer (NSCLC) with SMARCA4 deficiency represents a rare subset of lung tumors characterized by early metastasis, poor response to chemotherapy, and unfavorable prognosis. Established therapy strategies for SMARCA4-deficient NSCLC remain elusive. While immune checkpoint inhibitors have been proposed as a potential solution, their efficacy remains uncertain. Clinical factors such as tumor mutational burden (TMB), microsatellite instability, comutations, and programmed death-ligand 1 (PD-L1) expression may influence the treatment response of SMARCA4-deficient NSCLC. Additionally, PD-L1 expression on circulating tumor cells (CTCs) provides novel insights for monitoring, and its utility in SMARCA4-deficient NSCLC remains unexplored. The present report describes the case of a 71-year-old man diagnosed with SMARCA4-deficient NSCLC who had a history of heavy smoking and chronic cough. Imaging examination revealed metastatic lymph nodes. All serum tumor markers were elevated above the normal range. Histopathological and immunohistochemical analyses of the biopsy specimen from a primary lesion in the right upper lung demonstrated irregularly arranged tumor cells, SMARCA4 deficiency, and positive PD-L1 expression. Further next-generation sequencing confirmed SMARCA4 mutation, high TMB, and microsatellite stability (MSS). The patient received pembrolizumab treatment and experienced a sustained benefit for >40 months, with persistent PD-L1 expression on CTCs observed throughout the treatment. It was revealed that pembrolizumab therapy shows promise for patients with SMARCA4-deficient NSCLC with positive PD-L1 expression, high TMB, and MSS. Dynamic monitoring of PD-L1 status on CTCs may facilitate the assessment of the immunotherapy response, and the sustained positive PD-L1 expression on CTCs may imply continued benefit from immunotherapy for patients with SMARCA4-deficient NSCLC.</p>\",\"PeriodicalId\":7969,\"journal\":{\"name\":\"Anti-Cancer Drugs\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2025-09-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Anti-Cancer Drugs\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/CAD.0000000000001758\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Anti-Cancer Drugs","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/CAD.0000000000001758","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}
Pembrolizumab treatment in SMARCA4-deficient nonsmall cell lung cancer: high tumor mutational burden and programmed death-ligand 1(+) expression on circulating tumor cells for real-time monitoring: a case report.
Nonsmall cell lung cancer (NSCLC) with SMARCA4 deficiency represents a rare subset of lung tumors characterized by early metastasis, poor response to chemotherapy, and unfavorable prognosis. Established therapy strategies for SMARCA4-deficient NSCLC remain elusive. While immune checkpoint inhibitors have been proposed as a potential solution, their efficacy remains uncertain. Clinical factors such as tumor mutational burden (TMB), microsatellite instability, comutations, and programmed death-ligand 1 (PD-L1) expression may influence the treatment response of SMARCA4-deficient NSCLC. Additionally, PD-L1 expression on circulating tumor cells (CTCs) provides novel insights for monitoring, and its utility in SMARCA4-deficient NSCLC remains unexplored. The present report describes the case of a 71-year-old man diagnosed with SMARCA4-deficient NSCLC who had a history of heavy smoking and chronic cough. Imaging examination revealed metastatic lymph nodes. All serum tumor markers were elevated above the normal range. Histopathological and immunohistochemical analyses of the biopsy specimen from a primary lesion in the right upper lung demonstrated irregularly arranged tumor cells, SMARCA4 deficiency, and positive PD-L1 expression. Further next-generation sequencing confirmed SMARCA4 mutation, high TMB, and microsatellite stability (MSS). The patient received pembrolizumab treatment and experienced a sustained benefit for >40 months, with persistent PD-L1 expression on CTCs observed throughout the treatment. It was revealed that pembrolizumab therapy shows promise for patients with SMARCA4-deficient NSCLC with positive PD-L1 expression, high TMB, and MSS. Dynamic monitoring of PD-L1 status on CTCs may facilitate the assessment of the immunotherapy response, and the sustained positive PD-L1 expression on CTCs may imply continued benefit from immunotherapy for patients with SMARCA4-deficient NSCLC.
期刊介绍:
Anti-Cancer Drugs reports both clinical and experimental results related to anti-cancer drugs, and welcomes contributions on anti-cancer drug design, drug delivery, pharmacology, hormonal and biological modalities and chemotherapy evaluation. An internationally refereed journal devoted to the fast publication of innovative investigations on therapeutic agents against cancer, Anti-Cancer Drugs aims to stimulate and report research on both toxic and non-toxic anti-cancer agents. Consequently, the scope on the journal will cover both conventional cytotoxic chemotherapy and hormonal or biological response modalities such as interleukins and immunotherapy. Submitted articles undergo a preliminary review by the editor. Some articles may be returned to authors without further consideration. Those being considered for publication will undergo further assessment and peer-review by the editors and those invited to do so from a reviewer pool.