Lung Cancer: Targets and Therapy最新文献

{"title":"Innovative Techniques in Video-Assisted Thoracoscopic Surgery: Lu's Approach.","authors":"Baofeng Wang, Jiang Wang, Tongyu Sun, Yilin Ding, Shasha Li, Hengxiao Lu","doi":"10.2147/LCTT.S446418","DOIUrl":"10.2147/LCTT.S446418","url":null,"abstract":"<p><strong>Purpose: </strong>Lu's approach for video-assisted thoracoscopic surgery (LVATS), which derives from Uniportal Video-Assisted Thoracoscopic Surgery(UVATS), is a novel surgical approach for VATS and carries out micro-innovation for lung cancer resection. The objective of this study is to elucidate the safety, feasibility, and efficacy of this novel surgical approach.</p><p><strong>Patients and methods: </strong>The clinical data of patients with non-small cell lung cancer (NSCLC) who underwent a curative thoracoscopic lobectomy between Mar. 2021 and Mar. 2022, were retrospectively collected and analyzed. Patients were divided into the LVATS group and the UVATS group. Propensity score matching (PSM) was used to reduce selection bias and create two comparable groups. Perioperative variables were compared, and a p-value < 0.05 was deemed statistically significant.</p><p><strong>Results: </strong>A total of 182 patients were identified, among whom 86 patients underwent LVATS and 96 UVATS. Propensity matching produced 62 pairs in this retrospective study. There were no deaths during perioperative period. Patients in the LVATS group experienced a shorter operation time (88 (75, 106) VS 122 (97, 144) min, P <0.001), less intraoperative blood loss (20 (20, 30) VS 25 (20, 50) mL, P = 0.021), shorten incision length (2.50 (2.50, 2.50) VS 3.00 (3.00, 3.50) cm, P <0.001), and more drainage volume (460 (310, 660) VS 345 (225, 600) mL, P = 0.041) than patients in the UVATS group. There was not significant difference in the lymph node stations dissected (5 (4, 5) VS 5 (4, 5), P = 0.436), drainage duration (3 (3, 4) VS 3 (3, 4) days, P =0.743), length of postoperative hospital stay (4 (4, 5) VS 4 (4, 6) days, P = 0.608), VAS on the POD1 (4 (4, 4) VS 4 (4, 4), P=0.058) and POD3 (3 (3, 4) VS 4 (3, 4), P=0.219), and incidence of postoperative complications (P=0.521) between the two groups.</p><p><strong>Conclusion: </strong>Lu's approach for video-assisted thoracoscopic lobectomy is safe and feasible, potentially reducing surgery time, incision length, and intraoperative blood loss.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"15 ","pages":"9-17"},"PeriodicalIF":3.6,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10848822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139702880","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":"Stage as the Sole \"Biomarker\" for Adjuvant Pembrolizumab in Resected Stage IB to IIIA NSCLC without Considerations for PD-L1 Expression Level, ALK/EGFR Mutational Status, and Prior Adjuvant Chemotherapy per FDA Approval Indications of PEARLS/Keynote-091?","authors":"Misako Nagasaka, Saihong Ignatius Ou","doi":"10.2147/LCTT.S433195","DOIUrl":"https://doi.org/10.2147/LCTT.S433195","url":null,"abstract":"<p><p>One of the most recent advancements in NSCLC was the approval of immunotherapy in the adjuvant setting. Both atezolizumab and pembrolizumab have been approved for the use in early stage NSCLC patients post resection. As it broadens the options for our patients, multiple approvals in the same setting are generally welcomed. However, there were important differences in the two studies that led to the approvals and the data could be confusing. Here we review IMpower010, the study that led to the first approval of atezolizumab in the adjuvant setting with comparison to the Keynote-091 study evaluating pembrolizumab in the adjuvant setting, gaining the most recent FDA approval for adjuvant use in early stage NSCLC.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"14 ","pages":"101-109"},"PeriodicalIF":3.6,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10725831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138796896","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":"Single-Cell Profiling of Tumor-Associated Neutrophils in Advanced Non-Small Cell Lung Cancer.","authors":"Jinpeng Shi, Jiayu Li, Haowei Wang, Xuefei Li, Qi Wang, Chao Zhao, Lei Cheng, Ruoshuang Han, Peixin Chen, Haoyue Guo, Zhuoran Tang, Caicun Zhou, Zhemin Zhang, Fengying Wu","doi":"10.2147/LCTT.S430967","DOIUrl":"https://doi.org/10.2147/LCTT.S430967","url":null,"abstract":"<p><strong>Purpose: </strong>Neutrophils act as a non-negligible regulator in the initiation and progression of malignancies, playing bifacial roles in the process. Thus, to understand the heterogeneity of tumor-associated neutrophils (TANs) comprehensively in advanced non-small cell lung cancer (NSCLC) at single-cell resolution is necessary and urgent.</p><p><strong>Materials and methods: </strong>We applied single-cell RNA-sequencing (scRNA-seq) to portray the subtype-specific transcriptome landscape of TANs in advanced NSCLC using nine freshly obtained specimens. The scRNA-seq data were further processed for pseudo-time analysis to depict the developmental trajectory of TANs. Meanwhile, the interplay between TANs and other cell types within tumor microenvironment (TME) was revealed by intercellular interaction analysis.</p><p><strong>Results: </strong>Seven distinct TAN subtypes were defined, of which, the N₃ cluster was considered inflammatory phenotype expressing genes encoding multiple chemotactic cytokines, and correlated with inferior overall survival, indicating that N₃ might be a pro-tumorigenic TAN subtype. N₁ and N₅ clusters were considered to be well differentiated and mature neutrophils based on <i>CXCR2</i> expression and pseudo-time patterns, and both accounted for relatively high proportions in lung adenocarcinoma. In addition, genes related to neutrophil differentiation were discovered. We also found that TAN subtypes interacted most closely with macrophages through chemokine signaling pathways within TME.</p><p><strong>Conclusion: </strong>Our study refined TAN subtypes and mapped the transcriptome landscape of TANs at single-cell resolution in advanced NSCLC, collectively indicating the heterogeneity of TANs in NSCLC. Neutrophil differentiation- and maturation-related genes were also discovered, which shed light on different functions of TAN subclones in tumor immune escape, and may further provide novel targets for immunotherapy.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"14 ","pages":"85-99"},"PeriodicalIF":3.6,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10676108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138460706","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":"Co-Occurring EGFR S645C and EGFR L858R in a Patient with Lung Adenocarcinoma Induced Primary Resistance to Osimertinib.","authors":"Li Wang,&nbsp;Fei Quan,&nbsp;Zhen Guo,&nbsp;Zhongyu Lu,&nbsp;Duoxia Yang,&nbsp;Meiqi Shi","doi":"10.2147/LCTT.S431252","DOIUrl":"10.2147/LCTT.S431252","url":null,"abstract":"<p><p>Approximately 10-20% of patients demonstrate primary resistance to EGFR-TKIs, and different EGFR mutations vary in sensitivity to EGFR-TKIs. We report a case of a 78-year-old male with lung adenocarcinoma that EGFR L858R (AF = 1.32%) coexisting with EGFR S645C (AF = 7.13%) in his diagnosed tissues analyzed by NGS. The patient was primarily resistant to first-line osimertinib and rapidly progressed after pembrolizumab in combination with pemetrexed and bevacizumab, as demonstrated by persistently elevated CEA levels during treatment. ctDNA-based NGS analysis revealed loss of EGFR L858R while persistence of highly abundant EGFR S645C in the pleural fluid and plasma after treatment, suggesting that EGFR L858R may be a subclone. We provide the first clinical evidence of the primary resistance of EGFR S645C to osimertinib and emphasize the importance of identifying clones and subclones. Our patient did not respond to immunotherapy either, and preclinical studies have shown that EGFR S645C activates the MEK signaling pathway, the combination of EGFR-TKIs and MEK inhibitors may be effective.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"14 ","pages":"79-84"},"PeriodicalIF":3.6,"publicationDate":"2023-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6e/ba/lctt-14-79.PMC10576154.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41236581","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":"A Long Overdue Targeted Treatment for KRAS Mutations in NSCLC: Spotlight on Adagrasib.","authors":"Danielle Brazel,&nbsp;Zhaohui Arter,&nbsp;Misako Nagasaka","doi":"10.2147/LCTT.S383662","DOIUrl":"https://doi.org/10.2147/LCTT.S383662","url":null,"abstract":"<p><p>KRAS^G12C is one of the most common oncogenes in non-small cell lung cancer (NSCLC) and is associated with a poor prognosis. Historically, KRAS mutations have been difficult to target due to lack of binding sites and exceptionally high affinity for guanosine triphosphate/guanosine diphosphate (GTP/GDP). Recently, KRAS^G12C selective inhibitors have shown promising results in Phase I/II studies. Here we discuss the mechanism of action, pharmacokinetic and pharmacodynamic properties, efficacy, and tolerability of adagrasib (MRTX849).</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":" ","pages":"75-80"},"PeriodicalIF":3.6,"publicationDate":"2022-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7e/c9/lctt-13-75.PMC9662012.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40708267","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 Furmonertinib (Alflutinib, AST2818). The Swiss Army Knife (del19, L858R, T790M, Exon 20 Insertions, \"uncommon-G719X, S768I, L861Q\") Among the Third-Generation EGFR TKIs?","authors":"Shannon S Zhang,&nbsp;Sai-Hong Ignatius Ou","doi":"10.2147/LCTT.S385437","DOIUrl":"https://doi.org/10.2147/LCTT.S385437","url":null,"abstract":"<p><p>Osimertinib, a third-generation (3G) epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is now considered the standard of care for the first-line (1L) treatment of advanced <i>EGFR</i>+ NSCLC due to statistically significant improved progression-free survival (PFS) and overall survival (OS) compared with first-generation (1G) treatment from the FLAURA trial. Recently two other 3G EGFR TKIs (aumolertinib and furmonertinib) have been approved in China for treatment of <i>EGFR</i> T790M+ NSCLC. Randomized Phase 3 trials of these two 3G EGFR TKIs have also demonstrated PFS over gefitinib respectively. Among these two Chinese home-grown, 3G EGFR TKIs, furmonertinib seems to most closely resemble osimertinib in terms of dosing regimen, efficacy and adverse events profile. In this article, we reviewed the clinical activity and adverse events of furmonertinib at 80 mg daily (approved dose), potential usage of 160 mg daily for CNS metastasis in <i>EGFR</i>+ NSCLC, and usage of 160 mg or 240 mg daily in <i>EGFR</i> exon20 insertion positive (<i>EGFRex20ins</i>+) NSCLC patients.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":" ","pages":"67-73"},"PeriodicalIF":3.6,"publicationDate":"2022-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e0/7d/lctt-13-67.PMC9617553.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40659985","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":"Arginine Deprivation in SCLC: Mechanisms and Perspectives for Therapy.","authors":"Joséphine Carpentier,&nbsp;Iuliia Pavlyk,&nbsp;Uma Mukherjee,&nbsp;Peter E Hall,&nbsp;Peter W Szlosarek","doi":"10.2147/LCTT.S335117","DOIUrl":"https://doi.org/10.2147/LCTT.S335117","url":null,"abstract":"<p><p>Arginine deprivation has gained increasing traction as a novel and safe antimetabolite strategy for the treatment of several hard-to-treat cancers characterised by a critical dependency on arginine. Small cell lung cancer (SCLC) displays marked arginine auxotrophy due to inactivation of the rate-limiting enzyme argininosuccinate synthetase 1 (ASS1), and as a consequence may be targeted with pegylated arginine deiminase or ADI-PEG20 (pegargiminase) and human recombinant pegylated arginases (rhArgPEG, BCT-100 and pegzilarginase). Although preclinical studies reveal that ASS1-deficient SCLC cell lines are highly sensitive to arginine-degrading enzymes, there is a clear disconnect with the clinic with minimal activity seen to date that may be due in part to patient selection. Recent studies have explored resistance mechanisms to arginine depletion focusing on tumor adaptation, such as ASS1 re-expression and autophagy, stromal cell inputs including macrophage infiltration, and tumor heterogeneity. Here, we explore how arginine deprivation may be combined strategically with novel agents to improve SCLC management by modulating resistance and increasing the efficacy of existing agents. Moreover, recent work has identified an intriguing role for targeting arginine in combination with PD-1/PD-L1 immune checkpoint inhibitors and clinical trials are in progress. Thus, future studies of arginine-depleting agents with chemoimmunotherapy, the current standard of care for SCLC, may lead to enhanced disease control and much needed improvements in long-term survival for patients.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":" ","pages":"53-66"},"PeriodicalIF":3.6,"publicationDate":"2022-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a3/4b/lctt-13-53.PMC9462517.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33466130","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":"ORIENT-31 as the Sakigake “Charging Samurai” Born of IMpower150 but Will MARIPOSA-2 IMPRESS in the “Meiji Modernization” of Post-3G EGFR TKI Progression?","authors":"M. Nagasaka, S. Ou","doi":"10.2147/LCTT.S355503","DOIUrl":"https://doi.org/10.2147/LCTT.S355503","url":null,"abstract":"Abstract Tyrosine kinase inhibitors (TKIs) have become the preferred first line therapy for those patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. Given superior progression free survival (PFS) and overall survival (OS) when compared to earlier generations, third generation EGFR TKIs have become the first choice therapy in many parts of the world. Even though multiple strategies are in development to target both “on-target” and “off-target” resistance, the continuation of EGFR TKIs at the time of progression remains a controversial topic. This commentary focuses on both the ”classic” clinical trials of IMpower150 and IMPRESS and compares them to the recently reported ORIENT-31 and ongoing MARIPOSA-2 to discuss the future therapeutic strategies in the setting of progression post-third generation EGFR TKIs.","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"21 1","pages":"13 - 21"},"PeriodicalIF":3.6,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75702529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Update on Emerging Therapeutic Options for Malignant Pleural Mesothelioma","authors":"A. Davis, H. Ke, S. Kao, N. Pavlakis","doi":"10.2147/LCTT.S288535","DOIUrl":"https://doi.org/10.2147/LCTT.S288535","url":null,"abstract":"Abstract The treatment paradigm for malignant pleural mesothelioma (MPM) has changed little in the last 18 years. Radical intent treatment, consisting of surgical resection, radiotherapy and chemotherapy, has been offered to a highly select few; however, there is little randomised evidence to validate this approach. Prior to 2020 chemotherapy with platinum and an anti-folate was the only intervention with randomised evidence to demonstrate improved overall survival (OS) in MPM. No systemic therapy had been demonstrated to improve OS in the second line setting until 2020. The publication of the Checkmate 743 trial in 2021 demonstrated a survival benefit of combination immunotherapy over standard chemotherapy in newly diagnosed patients with MPM. This finding was shortly followed by the CONFIRM trial which demonstrates a modest but significant survival benefit of second line nivolumab versus placebo in patients having previously received standard chemotherapy. The results of these trials, recent biomarker directed therapy and chemotherapy adjuncts are discussed within this review. The integration of immunotherapy for the few patients in whom radical surgical therapy is intended is currently the subject of clinical trials and offers the prospect of improving outcomes in this rare but devastating disease.","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"23 1","pages":"1 - 12"},"PeriodicalIF":3.6,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83955144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spotlight on Trastuzumab Deruxtecan (DS-8201,T-DXd) for <i>HER2</i> Mutation Positive Non-Small Cell Lung Cancer.","authors":"Ibrahim Azar,&nbsp;Samer Alkassis,&nbsp;Jami Fukui,&nbsp;Fares Alsawah,&nbsp;Kalub Fedak,&nbsp;Mohammed Najeeb Al Hallak,&nbsp;Ammar Sukari,&nbsp;Misako Nagasaka","doi":"10.2147/LCTT.S307324","DOIUrl":"https://doi.org/10.2147/LCTT.S307324","url":null,"abstract":"<p><p>Human epidermal growth factor receptor 2 (<i>HER2</i>) is a proto-oncogene that, when mutated or overexpressed, plays an important role in oncogenesis. The landscape of <i>HER2</i>-positive breast cancer has changed dramatically over the past 2 decades with the FDA approval of a growing number of agents (antibodies, tyrosine kinase inhibitors, and antibody-drug conjugates) targeting the <i>HER2</i> receptor. <i>HER2</i> inhibition has also been approved for <i>HER2</i>-positive gastric cancer. <i>HER2</i> is amplified in 9% and mutated in 3% of lung cancer. Historically, <i>HER2</i>-targeted therapy for lung cancer with trastuzumab, pertuzumab, and trastuzumab emtansine has failed to demonstrate a survival benefit. Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug conjugate with a tetrapeptide linker, which delivers a topoisomerase I inhibitor with a drug-to-antibody ratio of 7~8. The potency of the active payload, as well as its significant bystander effect, resulted in significant anti-tumor activity. The DESTINY-Lung01 trial evaluated T-DXd in <i>HER2</i>-positive non-squamous non-small cell lung cancer (NSCLC) and reported a progression-free survival of 14 months in <i>HER2</i>-mutated NSCLC, earning its breakthrough designation by the FDA. In this review, we will discuss the structural characteristics, pharmacodynamics, and pharmacokinetics of T-DXd. We will also shed light on the preclinical and ongoing clinical trials of T-DXd along with future directions in the management of <i>HER2</i> positive lung cancer.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"12 ","pages":"103-114"},"PeriodicalIF":3.6,"publicationDate":"2021-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fc/bc/lctt-12-103.PMC8507417.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39538897","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}