Lung Cancer: Targets and Therapy最新文献

{"title":"Adagrasib in KRYSTAL-12 has Broken the <i>KRAS</i> ^G12C Enigma Code in Non-Small Cell Lung Carcinoma.","authors":"Faustine X Luo, Zhaohui Liao Arter","doi":"10.2147/LCTT.S490942","DOIUrl":"10.2147/LCTT.S490942","url":null,"abstract":"<p><p>Kirsten rat sarcoma viral oncogene homolog <i>(KRAS)</i> ^G12C-mutant non-small cell lung carcinoma (NSCLC) accounts for approximately 10-13% of advanced nonsquamous NSCLC cases in Western populations, presenting a significant therapeutic challenge owing to the difficulty of directly targeting KRAS. Adagrasib, an oral small-molecule covalent inhibitor, irreversibly and selectively targets KRAS^G12C in its inactive state. It received accelerated Food and Drug Administration (FDA) approval on December 12, 2022, following the KRYSTAL-1 Phase II trial. The Phase III KRYSTAL-12 trial demonstrated that adagrasib significantly improved median progression-free survival (mPFS) compared with docetaxel (HR, 0.58; 95% CI: 0.45-0.76; P<0.0001) and increased the intracranial objective response rate (ORR) to 40% in the central nervous system (CNS) evaluable population. This paper evaluates the clinical efficacy of adagrasib in <i>KRAS</i> ^G12C-mutated advanced NSCLC discussing its potential advantages over other inhibitors such as sotorasib. Despite not reaching the 6-month mPFS benchmark, adagrasib offers significant clinical benefits, particularly for the management of CNS metastases. In this pros and cons debate, we argue that adagrasib has broken the <i>KRAS</i> ^G12C enigma code in NSCLC.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"15 ","pages":"161-167"},"PeriodicalIF":5.1,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Outcomes with Lurbinectedin in Second Line and Beyond for Extensive Stage Small Cell Lung Cancer in Korea.","authors":"Joo Sung Shim, Youhyun Kim, Taeho Yuh, Jii Bum Lee, Hye Ryun Kim, Min Hee Hong, Byoung Chul Cho, Sun Min Lim","doi":"10.2147/LCTT.S485320","DOIUrl":"10.2147/LCTT.S485320","url":null,"abstract":"<p><strong>Purpose: </strong>Small-cell lung cancer (SCLC) accounts for approximately 10-15% of all lung cancers and is characterized by a high recurrence rate, early metastasis, and poor prognosis. Before the FDA approved lurbinectedin for SCLC that progressed on or after platinum-based chemotherapy in 2020, topotecan was the sole second-line option associated with hematological toxicities and modest efficacy. Lurbinectedin received conditional approval in Korea in September 2022 for metastatic SCLC progression, with the same indications. Real-world data on its efficacy remains scarce owing to its recent implementation.</p><p><strong>Patients and methods: </strong>Patients with metastatic SCLC who progressed on or after first-line therapy (n = 51) at Yonsei Cancer Center, Seoul, received lurbinectedin at 3.2 mg/m². Efficacy data, including tumor response, progression, survival, and demographics, were recorded.</p><p><strong>Results: </strong>A total of fifty-one patients received lurbinectedin between April 2023 and March 2024, with thirty-four patients being eligible for the assessment. At diagnosis, approximately one-third of the patients were female, 3% had a poor performance status with an Eastern Cooperative Oncology Group Performance Score (ECOG PS ≥ 2), and the median age was 68. Most patients (80%) had extensive disease. Overall objective response rate (ORR) and disease control rate (DCR) were 20% and 47%, respectively. The median progression-free survival (PFS) was 2.8 months, and the median overall survival (OS) was 3.3 months. Never smokers showed prolonged OS compared with current/former smokers (Smokers; 3.0 vs 7.3 months). Common adverse effects were nausea (53%), loss of appetite (24%), general weakness (18%), anemia (29%), neutropenia (12%), dizziness (6%), alopecia (6%), thrombocytopenia (3%), and pneumonia (3%). Overall, 24% of the patients experienced grade ≥3 adverse events (AEs), with the most common being anemia (9%) and neutropenia (9%).</p><p><strong>Conclusion: </strong>Real-world data suggest that lurbinectedin is a viable option for patients with SCLC who have progressed on or after platinum-based chemotherapy.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"15 ","pages":"149-159"},"PeriodicalIF":5.1,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NRG1 Fusions in NSCLC: Being eNRGy Conscious.","authors":"Brinda Gupta, Laura Gosa Barrett, Stephen V Liu","doi":"10.2147/LCTT.S464626","DOIUrl":"https://doi.org/10.2147/LCTT.S464626","url":null,"abstract":"<p><p>Fusions in neuregulin 1 (<i>NRG1</i>) are rare oncogenic drivers that occur across a number of tumor types, including non-small cell lung cancer (NSCLC). <i>NRG1</i> has an EGF-like domain that serves as a ligand for HER3 receptors, inducing heterodimerization, usually with HER2, and subsequent activation of oncogenic downstream signaling pathways. Emerging evidence suggests that NSCLC harboring <i>NRG1</i> fusions do not respond as well to standard therapeutic options including chemotherapy and immunotherapy, and prognosis is poor. Novel treatment approaches targeting the HER2/HER3 pathway are under investigation. Here, we discuss the biology and detection of <i>NRG1</i> fusions in NSCLC and promising targeted treatment strategies for tumors harboring the mutation.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"15 ","pages":"143-148"},"PeriodicalIF":5.1,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pulmonary Spindle Cell Carcinoma Mimicking Granulomatous Inflammation: A Rare Case Report and Brief Review of the Literature.","authors":"Qian Liu, Jun Zhang, Mingqin Wei, Xue Zhou, Hao Sun, Youhong Dong, Dongdong Zhang","doi":"10.2147/LCTT.S480969","DOIUrl":"10.2147/LCTT.S480969","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary spindle cell carcinoma (PSCC), a highly malignant tumor, often exhibits cell pleomorphism, a histopathological characteristic. Owing to its extremely low incidence, atypical imaging and clinical presentations, and insufficient awareness among clinicians, PSCC is often misdiagnosed, which results in delays in treatment. Herein, we reported a rare case of PSCC that was initially misdiagnosed as granulomatous inflammation.</p><p><strong>Case presentation: </strong>A 66-year-old male visited a local hospital with symptoms such as cough and hemoptysis. A computed tomography (CT) scan of the chest revealed a mass in his right lung, and no mediastinal lymphadenopathy was observed. Bronchoscopy showed no major abnormalities, and the results of fine needle aspiration biopsy showed granulomatous inflammation. Even though the patient received anti-infection treatment, his symptoms did not improve markedly. After two months, a follow-up CT scan of the lung showed a noticeably enlarged mass accompanied by multiple instances of mediastinal lymphadenopathy in the upper lobe of the right lung. Consequently, he underwent a second CT-guided lung biopsy at our hospital. The pathology report indicated PSCC. Due to financial constraints, genetic testing was not performed. Given his poor overall physical condition, the patient was unable to undergo systemic chemotherapy and instead received palliative radiotherapy. The prescribed radiotherapy dose for the right upper lobe lung cancer and multiple metastatic lymph nodes was 60 Gy, administered in 30 fractions. Unfortunately, he failed to adhere to scheduled follow-ups and succumbed to the disease 6 months later, as confirmed during a telephone follow-up.</p><p><strong>Conclusion: </strong>PSCC is a rare but highly malignant lung cancer. Multiple pathological biopsies are necessary to accurately and promptly diagnose the disease, which is crucial for early treatment intervention as well as improving patient prognosis.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"15 ","pages":"135-142"},"PeriodicalIF":5.1,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Redefining Recovery: The Transformative Impact of the ALINA Trial on Adjuvant Therapy for <i>ALK</i>-Positive Non-Small Cell Lung Cancer.","authors":"Zhaohui Liao Arter, Misako Nagasaka","doi":"10.2147/LCTT.S478054","DOIUrl":"10.2147/LCTT.S478054","url":null,"abstract":"<p><p>On April 18, 2024, the Food and Drug Administration approved alectinib as an adjuvant treatment for patients with anaplastic lymphoma kinase (<i>ALK</i>)-positive non-small cell lung cancer (NSCLC) after tumor resection. This approval was grounded in the outcomes of the ALINA trial, which demonstrated that alectinib significantly enhances disease-free survival compared to traditional platinum-based chemotherapy in the adjuvant setting. The ALINA trial is notable not just for advancing ALK tyrosine kinase inhibitors (TKIs) into the adjuvant setting but also for its innovative approach of comparing them to adjuvant chemotherapy, distinguishing it from other landmark trials.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"15 ","pages":"129-133"},"PeriodicalIF":5.1,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11367166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutation of <i>MET D1228N</i> as an Acquired Potential Mechanism of Crizotinib Resistance in NSCLC with <i>MET Y1003H</i> Mutation.","authors":"Jinlian Zhu, Jie Chen, Wei Liu, Junling Zhang, Yulan Gu","doi":"10.2147/LCTT.S467584","DOIUrl":"10.2147/LCTT.S467584","url":null,"abstract":"<p><p>Mesenchymal-epithelial transition (<i>MET</i>) gene has been identified as a promising target for treatments. However, different sites of the <i>MET</i> mutation show different effects to MET inhibition. Here, we reported a non-small cell lung cancer (NSCLC) patient harboring <i>MET Y1003H</i> mutation who achieved a durable partial response to crizotinib with a PFS of 22.4 months. Furthermore, we report for the first time the identification of <i>MET D1228N</i> as a possible mechanism of acquired resistance to crizotinib in a patient with <i>MET Y1003H</i> mutation during disease progression.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"15 ","pages":"123-128"},"PeriodicalIF":5.1,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11365520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spotlight on Patritumab Deruxtecan (HER3-DXd) from HERTHENA Lung01. Is a Median PFS of 5.5 Months Enough in Light of FLAURA-2 and MARIPOSA?","authors":"Zhaohui Liao Arter, Misako Nagasaka","doi":"10.2147/LCTT.S467169","DOIUrl":"10.2147/LCTT.S467169","url":null,"abstract":"<p><p>On December 22, 2023, the US Food and Drug Administration (FDA) approved the biologics license application for patritumab deruxtecan (HER3-DXd) for priority review. This treatment is aimed at adult patients with locally advanced or metastatic NSCLC with EGFR mutations, who have received at least two prior systemic therapies. Approval of patritumab deruxtecan would mark it as the first HER3 targeted therapy in the United States. This prioritization by the FDA is grounded in compelling results from the global Phase II HERTHENA-Lung01 trial, wherein HER3-DXd exhibited clinically meaningful efficacy, achieving a median progression-free survival (mPFS) of 5.5 months in patients with heavily treated EGFR-mutated NSCLC. A pivotal question remains: Is a mPFS of 5.5 months sufficient in the context of the evolving first-line landscape observed in the FLAURA-2 and MARIPOSA trials?</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"15 ","pages":"115-121"},"PeriodicalIF":5.1,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11247161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141622145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Top 20 <i>EGFR+</i> NSCLC Clinical and Translational Science Papers That Shaped the 20 Years Since the Discovery of Activating <i>EGFR</i> Mutations in NSCLC. An Editor-in-Chief Expert Panel Consensus Survey.","authors":"Sai-Hong Ignatius Ou, Xiuning Le, Misako Nagasaka, Thanyanan Reungwetwattana, Myung-Ju Ahn, Darren W T Lim, Edgardo S Santos, Elaine Shum, Sally C M Lau, Jii Bum Lee, Antonio Calles, Fengying Wu, Gilberto Lopes, Virote Sriuranpong, Junko Tanizaki, Hidehito Horinouchi, Marina C Garassino, Sanjay Popat, Benjamin Besse, Rafael Rosell, Ross A Soo","doi":"10.2147/LCTT.S463429","DOIUrl":"https://doi.org/10.2147/LCTT.S463429","url":null,"abstract":"<p><p>The year 2024 is the 20^th anniversary of the discovery of activating epidermal growth factor receptor (<i>EGFR</i>) mutations in non-small cell lung cancer (NSCLC). Since then, tremendous advances have been made in the treatment of NSCLC based on this discovery. Some of these studies have led to seismic changes in the concept of oncology research and spurred treatment advances beyond NSCLC, leading to a current true era of precision oncology for all solid tumors. We now routinely molecularly profile all tumor types and even plasma samples of patients with NSCLC for multiple actionable driver mutations, independent of patient clinical characteristics nor is profiling limited to the advanced incurable stage. We are increasingly monitoring treatment responses and detecting resistance to targeted therapy by using plasma genotyping. Furthermore, we are now profiling early-stage NSCLC for appropriate adjuvant targeted treatment leading to an eventual potential \"cure\" in early-stage <i>EGFR+</i> NSCLC which have societal implication on implementing lung cancer screening in never-smokers as most <i>EGFR+</i> NSCLC patients are never-smokers. All these advances were unfathomable in 2004 when the five papers that described \"discoveries\" of activating <i>EGFR</i> mutations (del19, L858R, exon 20 insertions, and \"uncommon\" mutations) were published. To commemorate this 20^th anniversary, we assembled a global panel of thoracic medical oncology experts to select the top 20 papers (publications or congress presentation) from the 20 years since this seminal discovery with December 31, 2023 as the cutoff date for inclusion of papers to be voted on. Papers ranked 21 to 30 were considered \"honorable mention\" and also annotated. Our objective is that these 30 papers with their annotations about their impact and even all the ranked papers will serve as \"syllabus\" for the education of future thoracic oncology trainees. Finally, we mentioned potential practice-changing clinical trials to be reported. One of them, LAURA was published online on June 2, 2024 was not included in the list of papers to be voted on but will surely be highly ranked if this consensus survery is performed again on the 25^th anniversay of the discovery <i>EGFR</i> mutations (i.e. top 25 papers on the 25 years since the discovery of activating <i>EGFR</i> mutations).</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"15 ","pages":"87-114"},"PeriodicalIF":5.1,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11208875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"\"ACHILLES\" Heel No More? Afatinib at 40 Mg Once Daily is Superior to Platinum-Based Chemotherapy in <i>EGFR</i> Uncommon (G719X, S768I, and L861Q) Mutations (ACHILLES/TORG1834).","authors":"Faustine X Luo, Sai-Hong Ignatius Ou","doi":"10.2147/LCTT.S461758","DOIUrl":"10.2147/LCTT.S461758","url":null,"abstract":"<p><p>Afatinib, a second-generation covalent EGFR TKI, has been approved for the treatment of the three \"uncommon\" <i>EGFR</i> mutations (G719X, S768I, and L861Q) based on one pooled retrospective analysis of three prospective trials (LUX-Lung 2, 3 and 6). The confirmed overall response rate, as assessed by independent radiology review, was 66% (95% confidence interval: 47-81). Among the 21 responders, the proportion of patients with response duration of ≥12 months was 52% and the proportion with response durations of ≥18 months was 33%. Of note, all patients received afatinib at 40 or 50 mg once daily which is higher than the approved dose of 40 mg once daily and the usual 30 mg once daily starting dose by most thoracic oncologists. Given the approval of afatinib for \"uncommon\" <i>EGFR</i> mutations was based on the limited number of patients analyzed, the retrospective nature of the analysis, lack of randomized phase 2 or 3 trial, there remains uncertainty as to whether afatinib, chemotherapy or other next-generation EGFR TKIs is the optimal treatment. This uncertainty also hinders the development of future treatment of these \"uncommon\" mutations because of the uncertainty that afatinib is the optimal treatment and hence should be the standard of care control arm in future randomized trials. Finally, the ACHILLES/TORG1834 provided us with the first randomized trial result that afatinib achieved superior progression-free survival over platinum-based chemotherapy (10.6 months vs 5.7 months, HR = 0.42; 95% CI: 0.256-0.694; P = 0.0007). However, ACHILLES should mostly be considered as phase 2 trial given the limited number (N = 109) of patients enrolled. Furthermore, the PFS benefit seemed to be with the 40 mg daily dose (HR = 0.128; 95% CI: 0.050-0.327) and not with the 30 mg daily dose (HR = 0.704; 95% CI: 0.352-1.406). Further investigation of the 30 once daily dosing for the treatment of uncommon <i>EGFR</i> mutations is needed.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"15 ","pages":"69-73"},"PeriodicalIF":3.6,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11112201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141086674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HMGB1 Expression Levels Correlate with Response to Immunotherapy in Non-Small Cell Lung Cancer.","authors":"Maria González-Cao, Xueting Cai, Jilian Wilhelmina Paulina Bracht, Xuan Han, Yang Yang, Carlos Pedraz-Valdunciel, Teresa Morán, Javier García-Corbacho, Andrés Aguilar, Reyes Bernabé, Pedro De Marchi, Luciane Sussuchi da Silva, Leticia Ferro Leal, Rui Manuel Reis, Jordi Codony-Servat, Eloisa Jantus-Lewintre, Miguel Angel Molina-Vila, Peng Cao, Rafael Rosell","doi":"10.2147/LCTT.S455034","DOIUrl":"10.2147/LCTT.S455034","url":null,"abstract":"<p><strong>Purpose: </strong>High-mobility group box 1 protein (HMGB1) is subject to exportin 1 (XPO1)-dependent nuclear export, and it is involved in functions implicated in resistance to immunotherapy. We investigated whether HMGB1 mRNA expression was associated with response to immune checkpoint inhibitors (ICI) in non-small cell lung cancer (NSCLC).</p><p><strong>Patients and methods: </strong>RNA was isolated from pretreatment biopsies of patients with advanced NSCLC treated with ICI. Gene expression analysis of several genes, including HMGB1, was conducted using the NanoString Counter analysis system (PanCancer Immune Profiling Panel). Western blotting analysis and cell viability assays in EGFR and KRAS mutant cell lines were carried out. Evaluation of the antitumoral effect of ICI in combination with XPO1 blocker (selinexor) and trametinib was determined in a murine Lewis lung carcinoma model.</p><p><strong>Results: </strong>HMGB1 mRNA levels in NSCLC patients treated with ICI correlated with progression-free survival (PFS) (median PFS 9.0 versus 18.0 months, P=0.008, hazard ratio=0.30 in high versus low HMGB1). After TNF-α stimulation, HMGB1 accumulates in the cytoplasm of PC9 cells, but this accumulation can be prevented by using selinexor or antiretroviral drugs. Erlotinib or osimertinib with selinexor in EGFR-mutant cells and trametinib plus selinexor in KRAS mutant abolish tumor cell proliferation. Selinexor with a PD-1 inhibitor with or without trametinib abrogates the tumor growth in the murine Lewis lung cancer model.</p><p><strong>Conclusion: </strong>An in-depth exploration of the functions of HMGB1 mRNA and protein is expected to uncover new potential targets and provide a basis for treating metastatic NSCLC in combination with ICI.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"15 ","pages":"55-67"},"PeriodicalIF":3.6,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11090191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}