{"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}
Ibrahim Azar, Samer Alkassis, Jami Fukui, Fares Alsawah, Kalub Fedak, Mohammed Najeeb Al Hallak, Ammar Sukari, Misako Nagasaka
{"title":"Spotlight on Trastuzumab Deruxtecan (DS-8201,T-DXd) for <i>HER2</i> Mutation Positive Non-Small Cell Lung Cancer.","authors":"Ibrahim Azar, Samer Alkassis, Jami Fukui, Fares Alsawah, Kalub Fedak, Mohammed Najeeb Al Hallak, Ammar Sukari, 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}
{"title":"Spotlight on Sotorasib (AMG 510) for <i>KRAS</i> <sup>G12C</sup> Positive Non-Small Cell Lung Cancer.","authors":"Shannon S Zhang, Misako Nagasaka","doi":"10.2147/LCTT.S334623","DOIUrl":"https://doi.org/10.2147/LCTT.S334623","url":null,"abstract":"<p><p>Mutations in codon 12 of <i>KRAS</i> have been identified in 13% of non-small cell lung cancer patients. Developing targeted therapies against <i>KRAS<sup>G12C</sup></i> mutation has proven to be challenging due to the abundance of GTP in the cytoplasm, rapid hydrolysis of GTP, and difficulty designing small molecules to achieve sufficient concentration for <i>KRAS</i> inhibition. Based on promising results in both preclinical and clinical trials, sotorasib, a novel <i>KRAS<sup>G12C</sup></i> inhibitor, was given conditional approval by the FDA in May 2021. The Phase I portion of the clinical trial produced 32% confirmed response with 56% of patients with stable disease. About 91.2% of patients who received the highest dose of 960mg daily achieved disease control. The Phase II portion, which used 960mg daily dosing resulted in 37.1% of patients with confirmed response and 80.6% of patients with disease control. Both phase I and phase II had similar progression-free survival, in 6.3 months and 6.8 months, respectively. In both phases, grade 4 adverse events occurred in only one patient. The most common adverse events were elevations in LFTs, which down-trended upon dose reduction and steroid treatment. While the conditional approval of sotorasib was a major breakthrough for those patients harboring <i>KRAS<sup>G12C</sup></i> mutations, resistance mutations to sotorasib are increasingly common. Many proposals have been made to address this, such as the use of combination therapy for synthetic lethality, which are producing encouraging results. Here, we explore in further detail the development of sotorasib, its efficacy, mechanism of resistance, and strategies to overcome these resistances.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"12 ","pages":"115-122"},"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/ba/d9/lctt-12-115.PMC8504654.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39538965","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}
Giannis Mountzios, Sofia Lampaki, Georgia-Angeliki Koliou, Athanassios Vozikis, Ioannis Kontogiorgos, Panagiotis Papantoniou, Margarita-Ioanna Koufaki, Eleni Res, Anastasios Boutis, Athina Christopoulou, Nicoleta Pastelli, Anastasios Grivas, Gerasimos Aravantinos, Efthalia Lalla, Georgios Oikonomopoulos, Anna Koumarianou, Dionisios Spyratos, Dimitrios Bafaloukos, Georgios Rigakos, Pavlos Papakotoulas, George Fountzilas, Helena Linardou
{"title":"An Observational Study to Assess the Molecular Epidemiology and Direct Medical Costs of Epidermal Growth Factor Receptor (EGFR) Mutations in Patients with Advanced EGFR Mutation-Positive Non-Small Cell Lung Cancer Treated with Afatinib in Real-World Clinical Settings in Greece.","authors":"Giannis Mountzios, Sofia Lampaki, Georgia-Angeliki Koliou, Athanassios Vozikis, Ioannis Kontogiorgos, Panagiotis Papantoniou, Margarita-Ioanna Koufaki, Eleni Res, Anastasios Boutis, Athina Christopoulou, Nicoleta Pastelli, Anastasios Grivas, Gerasimos Aravantinos, Efthalia Lalla, Georgios Oikonomopoulos, Anna Koumarianou, Dionisios Spyratos, Dimitrios Bafaloukos, Georgios Rigakos, Pavlos Papakotoulas, George Fountzilas, Helena Linardou","doi":"10.2147/LCTT.S318007","DOIUrl":"https://doi.org/10.2147/LCTT.S318007","url":null,"abstract":"<p><strong>Purpose: </strong>Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the preferred first-line option for patients with advanced, EGFR-mutant non-small cell lung cancer (NSCLC). Afatinib, a second-generation irreversible EGFR-TKI, has been extensively used in Greece in this setting; however, real-world data regarding molecular epidemiology and financial implications of afatinib use are lacking.</p><p><strong>Materials and methods: </strong>This was an observational, non-interventional, multicenter, retrospective cohort study, based on real-world data collected from the medical charts/records of patients treated with afatinib between 15/03/2015 and 25/06/2020 and were recorded on a web-based data capture system. Cox models were used to assess the prognostic significance of clinicopathological parameters with respect to clinical outcomes of interest. Cost analysis was conducted from a public third-payer perspective, and only direct medical costs reimbursed by the payer were considered.</p><p><strong>Results: </strong>A total of 59 patients were treated with afatinib for their EGFR mutation-positive advanced NSCLC; the median age was 61 years (range: 37-91). Performance status was zero in 61%, and brain metastases were present in 13.6%. Forty-four patients (74.6%) had a deletion in exon 19 only, while nine (15.3%) had a mutation in exon 21, 8 of them in L858R and one in L861Q. At a median follow-up of 41.8 months (95% CI 35.9-51.4), the median PFS was 14.3 months (95% CI 12.2-16.4), and the median OS was 29 months (95% CI 25.6-33.4). Corresponding values for patients with deletion 19 only were 14.3 months (95% CI 11.5-18.5) and 28.1 months (95% CI 21.1-32.6), respectively. The mean expenditure for the treatment of each patient equals €25,333.68; with €21,865.06 being attributed to drug acquisition costs, €3325.35 to monitoring costs and €143.27 to adverse event treatment-related costs.</p><p><strong>Conclusion: </strong>Long-term data in the real-world setting in Greece confirm activity, tolerability and cost-effectiveness of afatinib as first-line treatment of patients with advanced EGFR-mutant NSCLC.</p><p><strong>Clinical trial registration: </strong>Clinicaltrials.gov NCT04640870.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"12 ","pages":"93-102"},"PeriodicalIF":3.6,"publicationDate":"2021-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/23/a1/lctt-12-93.PMC8415762.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39409401","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":"An Update on the Use of Exhaled Breath Analysis for the Early Detection of Lung Cancer.","authors":"Nir Peled, Vered Fuchs, Emily H Kestenbaum, Elron Oscar, Raul Bitran","doi":"10.2147/LCTT.S320493","DOIUrl":"https://doi.org/10.2147/LCTT.S320493","url":null,"abstract":"<p><p>Lung cancer has historically been the main responsible for cancer associated deaths. Owing to this is our current inability to screen for and diagnose early pathological findings, preventing us from a timely intervention when cure is still achievable. Over the last decade, together with the extraordinary progress in therapeutical alternatives in the field, there has been an ongoing search for a biomarker that would allow for this. Numerous technologies have been developed but their clinical application is yet to come. In this review, we provide an update on volatile organic compounds, a non-invasive method that can hold the key for detecting early metabolic pathway changes in carcinogenesis. For its compilation, web-based search engines of scientific literature such as PubMed were explored and reviewed, using articles, research, and papers deemed meaningful by authors discretion. After a brief description, we depict how this technique can complement current methods and present the value of electronic noses in the identification of the \"breathprint\". Lastly, we bring some of the latest updates in the field together with the current limitations and final remarks.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"12 ","pages":"81-92"},"PeriodicalIF":3.6,"publicationDate":"2021-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bf/ca/lctt-12-81.PMC8378913.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39341046","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 Mobocertinib (TAK-788) in NSCLC with <i>EGFR</i> Exon 20 Insertion Mutations.","authors":"Shannon S Zhang, Viola W Zhu","doi":"10.2147/LCTT.S307321","DOIUrl":"https://doi.org/10.2147/LCTT.S307321","url":null,"abstract":"<p><p>The <i>EGFR</i> exon 20 insertion (<i>EGFR</i>ex20ins) mutations are the third most common <i>EGFR</i> mutations seen in non-small cell lung cancer (NSCLC). More than 50 variants of <i>EGFR</i>ex20ins mutations have been identified with A767_V769dupASV being the most common variant across multiple surveys. Treatment with currently available EGFR tyrosine kinase inhibitors (TKIs) including osimertinib is generally ineffective. Amivantamab (JNJ-372), a bispecific monoclonal antibody against EGFR and MET, has recently been approved by the US FDA for patients with advanced or metastatic NSCLC harboring <i>EGFR</i>ex20ins mutations after disease progression on platinum-based chemotherapy. Among all the TKIs in clinical development, mobocertinib (TAK-788) has been granted priority review by the FDA for the same indication as amivantamab. Here, we provide a concise review on mobocertinib, with a focus on its chemical structure, preclinical data, and phase 1/2 trial results. Future directions will likely focus on combination approach such as TKI plus chemotherapy in the first-line setting, designing drugs with CNS activity, and exploring disease characteristics of various <i>EGFR</i>ex20ins mutation variants and how they may affect treatment response.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"12 ","pages":"61-65"},"PeriodicalIF":3.6,"publicationDate":"2021-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5b/f8/lctt-12-61.PMC8286072.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39203180","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":"Lung Cancer with <i>MET</i> exon 14 Skipping Mutation: Genetic Feature, Current Treatments, and Future Challenges.","authors":"Toshio Fujino, Kenichi Suda, Tetsuya Mitsudomi","doi":"10.2147/LCTT.S269307","DOIUrl":"https://doi.org/10.2147/LCTT.S269307","url":null,"abstract":"<p><p><i>MET</i> exon 14 skipping mutation (<i>MET</i>∆ex14) is present about 3% of non-small cell lung cancers (NSCLCs). NSCLC patients with <i>MET</i>∆ex14 are characterized by an average age of over 70 years at diagnosis, a smoking history and a higher frequency in pleomorphic carcinoma and adenosquamous cell carcinoma than in adenocarcinoma. It has also been reported that NSCLCs with <i>MET</i>∆ex14 often have codriver alterations such as <i>EGFR</i> amplification (6-28%), <i>FGFR1</i> alterations (5-17%), <i>KRAS</i> alterations (~8%), <i>BRAF</i> alterations (~21%), or <i>PIK3CA</i> mutation/amplification (~14%). In 2020, the approval of two MET-tyrosine kinase inhibitors (TKIs), capmatinib and tepotinib, for NSCLCs carrying <i>MET</i>∆ex14 dawned a new era for MET-targeted therapy. These drugs yielded progression-free survival of 5.4-12.4 months in clinical trials; however, it has also been reported that one-third to half of patients show inherent resistance to MET-TKIs. In addition, the emergence of acquired resistance to MET-TKIs is inevitable. In this review, we summarize the clinical and molecular characteristics of NSCLCs with <i>MET</i>∆ex14, the efficacy and safety of capmatinib and tepotinib, the inherent and acquired resistance mechanisms to MET-TKIs, and new treatment strategies for NSCLCs with <i>MET</i>∆ex14 in the near future.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"12 ","pages":"35-50"},"PeriodicalIF":3.6,"publicationDate":"2021-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ed/5b/lctt-12-35.PMC8290191.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39210151","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":"Recognizing Prognostic and Predictive Biomarkers in the Treatment of Non-Small Cell Lung Cancer (NSCLC) with Immune Checkpoint Inhibitors (ICIs).","authors":"Nicholas Giustini, Lyudmila Bazhenova","doi":"10.2147/LCTT.S235102","DOIUrl":"https://doi.org/10.2147/LCTT.S235102","url":null,"abstract":"<p><p>Immunotherapy plays a central role in the treatment of NSCLC and biomarkers predicting response to ICIs are valuable therapeutic tools. Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) is integral in therapy selection as its positive predictive nature to ICIs in the metastatic setting is well documented. Tumor mutational burden (TMB) has undergone much study and, while results are somewhat mixed, there is evidence for its positive predictive value with ICI use. Additional markers such as tumor-infiltrating lymphocytes (TILs), gene expression profiling (GEP), mismatch repair (MMR) and microsatellite instability (MSI), somatic mutations, neutrophil to leukocyte ratio (NLR), smoking history, medication history, and immune-related adverse event (irAE) development can further guide clinicians.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"12 ","pages":"21-34"},"PeriodicalIF":3.6,"publicationDate":"2021-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/24/39/lctt-12-21.PMC8006757.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25551175","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}
Aaron C Tan, Tracy J Loh, Xue Lin Kwang, Gek San Tan, Kiat Hon Lim, Daniel S W Tan
{"title":"Novel Therapies for Metastatic Non-Small Cell Lung Cancer with MET Exon 14 Alterations: A Spotlight on Capmatinib.","authors":"Aaron C Tan, Tracy J Loh, Xue Lin Kwang, Gek San Tan, Kiat Hon Lim, Daniel S W Tan","doi":"10.2147/LCTT.S263610","DOIUrl":"https://doi.org/10.2147/LCTT.S263610","url":null,"abstract":"<p><p>MET exon 14 (METex14) alterations are now an established therapeutically tractable target in non-small cell lung cancer (NSCLC). Recently reported trials of several MET tyrosine kinase inhibitors (TKI) in this patient population have demonstrated promising efficacy data in both the treatment naïve and pre-treated settings and have led to regulatory approvals. This review will focus on practical diagnostic considerations for METex14 alterations, the trial evidence for capmatinib in this molecular subset including dosing and toxicity management, and the future therapeutic landscape of METex14 altered NSCLC.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"12 ","pages":"11-20"},"PeriodicalIF":3.6,"publicationDate":"2021-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5c/2f/lctt-12-11.PMC7987308.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25526405","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}
Danlei Yu, Wen Zhao, Karin A Vallega, Shi-Yong Sun
{"title":"Managing Acquired Resistance to Third-Generation EGFR Tyrosine Kinase Inhibitors Through Co-Targeting MEK/ERK Signaling.","authors":"Danlei Yu, Wen Zhao, Karin A Vallega, Shi-Yong Sun","doi":"10.2147/LCTT.S293902","DOIUrl":"https://doi.org/10.2147/LCTT.S293902","url":null,"abstract":"<p><p>Although epidermal growth factor receptor (EGFR)-targeted therapy has improved clinical outcomes of patients with advanced non-small-cell lung cancer (NSCLC) carrying activating EGFR mutations, the development of acquired resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs), including the promising third-generation ones, results in disease progression and has become an unavoidable problem that limits patient long-term benefit. The third-generation EGFR-TKIs, osimertinib and almonertinib, are now approved for the treatment of advanced NSCLC patients harboring activating EGFR mutations (first-line) and/or the resistant T790M mutation (second-line). Clinically, appropriate management of acquired resistance to third-generation EGFR-TKIs will substantially improve their long-term efficacy against EGFR-mutant NSCLC. Recent preclinical and clinical studies suggest that activation of the Ras/Raf/MEK/ERK signaling pathway may be an important resistance mechanism and accordingly co-targeting this pathway effectively overcomes and abrogates acquired resistance to third-generation EGFR-TKIs. This review focuses on discussing the scientific rationale for and potential of co-targeting MEK/ERK signaling in delaying and overcoming acquired resistance to third-generation EGFR-TKIs, particularly osimertinib.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"12 ","pages":"1-10"},"PeriodicalIF":3.6,"publicationDate":"2021-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5d/48/lctt-12-1.PMC7872905.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25360269","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}