Lung Cancer: Targets and Therapy最新文献

{"title":"Polo-like kinase 1 inhibition in NSCLC: mechanism of action and emerging predictive biomarkers","authors":"J. Stratmann, M. Sebastian","doi":"10.2147/LCTT.S177618","DOIUrl":"https://doi.org/10.2147/LCTT.S177618","url":null,"abstract":"Abstract Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. Due to often unspecific disease symptoms, locally advanced or metastatic disease is diagnosed in the majority of all cases. Palliative treatment options comprise of conventional cytotoxic agents, immunotherapy with checkpoint inhibitors and the use of specific small-molecule tyrosine kinase inhibitors (TKI). However, these TKIs are mainly restricted to a small proportion of patients with lung cancer that harbor activating driver mutations. Still, the effectiveness and favorable safety profile of these compounds have prompted a systematic search for specific driver mechanisms of tumorigenesis and moreover the development of corresponding kinase inhibitors. In recent years, the Polo-like kinase (PLK) family has emerged as a key regulator in mitotic regulation. Its role in cell proliferation and the frequently observed overexpression in various tumor entities have raised much interest in basic and clinical oncology aiming to attenuate tumor growth by targeting the PLK. In this review, we give a comprehensive summary on the (pre-) clinical development of the different types of PLK inhibitors in lung cancer and summarize their mechanisms of action, safety and efficacy data and give an overview on translational research aiming to identify predictive biomarkers for a rational use of PLK inhibitors.","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"89 1","pages":"67 - 80"},"PeriodicalIF":3.6,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80329423","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":"Impact of smoking on frequency and spectrum of K-RAS and EGFR mutations in treatment naive Indonesian lung cancer patients","authors":"N. Masykura, J. Zaini, E. Syahruddin, S. Andarini, A. Hudoyo, Refniwita Yasril, A. Ridwanuloh, Heriawaty Hidajat, F. Nurwidya, A. Utomo","doi":"10.2147/LCTT.S180692","DOIUrl":"https://doi.org/10.2147/LCTT.S180692","url":null,"abstract":"Background: Indonesia has the highest cigarette consumption in the world. We explored the clinical impact of smoking on the prevalence of EGFR and K-RAS mutations and survival in this prospective study. Methods: 143 treatment naive lung cancer patients were recruited from Persahabatan Hospital, a national tertiary hospital. DNA from cytological specimens had been extracted and genotyped for both EGFR and K-RAS mutations using a combination of PCR high resolution melting, restriction fragment length polymorphism (RFLP) and direct DNA sequencing. Results: EGFR mutation frequency in never smokers (NS) and ever smokers (ES) were 75% and 56% (p = 0.0401), respectively. In this cohort, the overall K-RAS mutation rate was 7%. Neither gender nor smoking history were associated with K-RAS mutation significantly. However, K-RAS transversion mutations were more common in male ES than transition mutations. Smoking history did not affect EGFR and K-RAS mutation frequencies in women. Concurrent EGFR/K-RAS mutation rate was 2.8% (4 of 143 patients). Four out of 91 EGFR mutation positive patients (4.4%) had simultaneous K-RAS mutation. Conclusions: In region where cigarette consumption is prevalent, smoking history affected frequencies of EGFR and K-RAS mutations, mainly in males.","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"9 1","pages":"57 - 66"},"PeriodicalIF":3.6,"publicationDate":"2019-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82581928","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":"Combination pembrolizumab plus chemotherapy: a new standard of care for patients with advanced non-small-cell lung cancer.","authors":"Frank Weinberg,&nbsp;Shirish Gadgeel","doi":"10.2147/LCTT.S176391","DOIUrl":"https://doi.org/10.2147/LCTT.S176391","url":null,"abstract":"<p><p>Until recently, the treatment of patients with advanced non-small-cell lung cancer (NSCLC) whose tumors did not have a targetable genetic alteration was cytotoxic chemotherapy alone. This treatment provided only modest survival benefit. The introduction of immune checkpoint inhibitors targeting programmed cell death 1 protein (PD-1) signaling pathway in the treatment of patients with NSCLC has had significant effect on patient survival. Atezolizumab, nivolumab and pembrolizumab have been shown to be superior to chemotherapy in patients with recurrent NSCLC. Recently, pembrolizumab has been combined with chemotherapy in the front-line setting and has demonstrated an improvement in overall survival in NSCLC patients as compared to chemotherapy alone. In this review we will focus on the clinical trials that led to approval of combination pembrolizumab and chemotherapy as first-line treatment for patients with advanced NSCLC as well as discuss other combinations of immunotherapy and chemotherapy that have also been evaluated.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"10 ","pages":"47-56"},"PeriodicalIF":3.6,"publicationDate":"2019-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S176391","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37361960","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":"Pain management in patients with malignant mesothelioma: challenges and solutions.","authors":"J Saunders,&nbsp;M Ashton,&nbsp;C Hall,&nbsp;B Laird,&nbsp;N MacLeod","doi":"10.2147/LCTT.S192558","DOIUrl":"https://doi.org/10.2147/LCTT.S192558","url":null,"abstract":"<p><p>Malignant pleural mesothelioma (MPM) is an aggressive cancer with a considerable symptom burden and poor prognosis. Focus on maintaining patients' quality of life and pain control is therefore paramount. Pain management in MPM is complex due to its multifactorial etiology resulting from direct tumor infiltration of the surrounding soft tissue, bone, and encasement of the intercostal nerves. A variety of treatment modalities, including pharmacological and non-pharmacological options, are often required to achieve adequate pain control in this challenging disease. This review article examines the current challenges and solutions available for pain management in MPM.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"10 ","pages":"37-46"},"PeriodicalIF":3.6,"publicationDate":"2019-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S192558","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37194559","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":"Targeting RET-rearranged non-small-cell lung cancer: future prospects.","authors":"Giuseppe Bronte,&nbsp;Paola Ulivi,&nbsp;Alberto Verlicchi,&nbsp;Paola Cravero,&nbsp;Angelo Delmonte,&nbsp;Lucio Crinò","doi":"10.2147/LCTT.S192830","DOIUrl":"https://doi.org/10.2147/LCTT.S192830","url":null,"abstract":"<p><p>Non-small-cell lung cancer (NSCLC) patients with mutated or rearranged oncogene drivers can be treated with upfront selective inhibitors achieving higher response rates and longer survival than chemotherapy. The RET gene can undergo chromosomal rearrangements in 1%-2% of all NSCLC patients, involving various upstream fusion partners such as KIF5B, CCDC6, NCOA4, and TRIM33. Many multikinase inhibitors are active against rearranged RET. Cabozantinib, vandetanib, sunitinib, lenvatinib, and nintedanib achieved tumor responses in about 30% of these patients in retrospective studies. Prospective phase II trials investigated the activity and toxicity of cabozantinib, vandetanib, sorafenib, and lenvatinib, and did not reach significantly higher response rates. VEGFR and EGFR inhibition represented the main ways of developing off-target toxicity. An intrinsic resistance emerged according to the type of RET fusion partners, as KIF5B-RET fusion is the most resistant. Also acquired mutations in rearranged RET oncogene developed as resistance to these multikinase inhibitors. Interestingly, RET fusions have been found as a resistance mechanism to EGFR-TKIs in EGFR-mutant NSCLC patients. The combination of EGFR and RET inhibition can overcome this resistance. The limitations in terms of activity and tolerability of the various multikinase inhibitors prompted the investigation of new highly selective RET inhibitors, such as RXDX-105, BLU-667, and LOXO-292. Some data emerged about intracranial antitumor activity of BLU-667 and LOXO-292. If these novel drugs will achieve high activity in RET rearranged NSCLC, also these oncogene-addicted tumors can undergo a significant survival improvement.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"10 ","pages":"27-36"},"PeriodicalIF":3.6,"publicationDate":"2019-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S192830","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37134879","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":"Differential response to a combination of full-dose osimertinib and crizotinib in a patient with <i>EGFR</i>-mutant non-small cell lung cancer and emergent <i>MET</i> amplification.","authors":"Viola W Zhu,&nbsp;Alexa B Schrock,&nbsp;Siraj M Ali,&nbsp;Sai-Hong Ignatius Ou","doi":"10.2147/LCTT.S190403","DOIUrl":"https://doi.org/10.2147/LCTT.S190403","url":null,"abstract":"<p><p>Exploring resistance mechanisms in patients with <i>EGFR</i>-mutant non-small-cell lung cancer (NSCLC) upon disease progression on EGFR tyrosine kinase inhibitors (TKIs) has been an area of great interest as it may lead to effective next-line treatment strategies. Here we report a case of emergent <i>MET</i> amplification detected in a tumor sample from a patient with NSCLC harboring EGFR L858R mutation after disease progression on erlotinib. The patient subsequently had a sustained partial response to a combination of full-dose osimertinib and crizotinib with excellent tolerance but eventually had central nervous system (CNS) progression. Comprehensive genomic profiling performed on the resected brain sample continued to demonstrate <i>MET</i> amplification as an acquired resistance mechanism. A review of literature shows several groups have utilized similar combination regimens (erlotinib or osimertinib + crizotinib or cabozantinib), albeit with various dosing to target <i>MET</i> alterations in patients with <i>EGFR</i>-mutant NSCLC. As more actionable resistance mechanisms are identified, we envision combination TKI therapy will be readily adopted in clinical practice. Our case report adds to a growing body of evidence that combination osimertinib and crizotinib should be recommended to <i>EGFR</i>-mutant NSCLC patients with emergent <i>MET</i> amplification as acquired resistance. More importantly, as crizotinib has limited brain penetration, developing next-generation MET inhibitors with better CNS activity is urgently needed.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"10 ","pages":"21-26"},"PeriodicalIF":3.6,"publicationDate":"2019-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S190403","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37064771","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":"Outcome of uncommon EGFR mutation positive newly diagnosed advanced non-small cell lung cancer patients: a single center retrospective analysis.","authors":"Shruti Kate,&nbsp;Anuradha Chougule,&nbsp;Amit Joshi,&nbsp;Vanita Noronha,&nbsp;Vijay Patil,&nbsp;Rohit Dusane,&nbsp;Leena Solanki,&nbsp;Priyanka Tiwrekar,&nbsp;Vaishakhi Trivedi,&nbsp;Kumar Prabhash","doi":"10.2147/LCTT.S181406","DOIUrl":"https://doi.org/10.2147/LCTT.S181406","url":null,"abstract":"<p><strong>Background: </strong>The significance of uncommon EGFR mutations in newly diagnosed advanced non-small-cell lung cancer (NSCLC) patients is incompletely known. We aimed to analyze the demographic profile, outcome, and treatment attributes of these patients.</p><p><strong>Patients and methods: </strong>We retrospectively surveyed 5,738 advanced NSCLC patients who underwent EGFR testing in our center from 2013 to 2017 by in-house primer probes on real time PCR platform. Descriptive data were accumulated from electronic medical records. Survival plot was calculated using Kaplan-Meier method and compared between groups using log-rank test.</p><p><strong>Results: </strong>Out of 1,260 EGFR mutation-positive patients, 83 (6.58%) had uncommon mutations in isolation or in various combinations. Uncommon mutations were more frequent in men, never-smokers, and adenocarcinomas. Overall, exon 18 G719X, exon 20 insertion, exon 20 T790M, exon 20 S768I, and exon 21 (L858R/L861Q) were present in 9.6%, 19.3%, 12%, 3.6%, and 3.6% patients, respectively. Dual mutation positivity was found in 50.6% patients. On classifying patients as per tyrosine kinase inhibitor (TKI) sensitivity, it was found that majority of the patients had a combination TKI sensitive and insensitive mutations. The median duration of follow-up was 13 months. Five patients were lost to follow-up. Median progression-free survival on first line therapy was 6.7 months (95% CI: 4.8-8.5). Median overall survival (OS) of patients who received TKI during the course of their disease was 20.2 months (95% CI: 11.4-28.9). Median overall survival (mOS) of the entire cohort was 15.8 months (95% CI: 10.1-21.5). Among all uncommon mutations, patients with dual mutations did better, with an mOS time of 22.6 months (95% CI: 8.2-37.0, <i>P</i>=0.005). It was observed that TKI sensitive/TKI insensitive dual mutations had a superior OS of 28.2 months (95% CI: 15.2-41.2, <i>P</i>=0.039) as compared to TKI sensitive and TKI insensitive EGFR mutations.</p><p><strong>Conclusion: </strong>Uncommon EGFR mutations constitute a heterogeneous group, hence, it is imperative to understand each subgroup more to define optimal treatment.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"10 ","pages":"1-10"},"PeriodicalIF":3.6,"publicationDate":"2019-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S181406","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36975570","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":"Clinical outcomes following advanced respiratory motion management (respiratory gating or dynamic tumor tracking) with stereotactic body radiation therapy for stage I non-small-cell lung cancer.","authors":"Paul Aridgides,&nbsp;Tamara Nsouli,&nbsp;Rishabh Chaudhari,&nbsp;Russell Kincaid,&nbsp;Paula F Rosenbaum,&nbsp;Sean Tanny,&nbsp;Michael Mix,&nbsp;Jeffrey Bogart","doi":"10.2147/LCTT.S175168","DOIUrl":"https://doi.org/10.2147/LCTT.S175168","url":null,"abstract":"<p><strong>Purpose: </strong>To report the outcomes of stereotactic body radiation therapy (SBRT) for stage I non-small-cell lung cancer (NSCLC) according to respiratory motion management method.</p><p><strong>Methods: </strong>Patients with stage I NSCLC who received SBRT from 2007 to 2015 were reviewed. Computed tomography (CT) simulation with four-dimensional CT was performed for respiratory motion assessment. Tumor motion >1 cm in the craniocaudal direction was selectively treated with advanced respiratory management: either respiratory gating to a pre-specified portion of the respiratory cycle or dynamic tracking of an implanted fiducial marker. Comparisons were made with internal target volume approach, which treated all phases of respiratory motion.</p><p><strong>Results: </strong>Of 297 patients treated with SBRT at our institution, 51 underwent advanced respiratory management (48 with respiratory gating and three with tumor tracking) and 246 underwent all-phase treatment. Groups were similarly balanced with regard to mean age (<i>P</i>=0.242), tumor size (<i>P</i>=0.315), and histology (<i>P</i>=0.715). Tumor location in the lower lung lobes, as compared to middle or upper lobes, was more common in those treated with advanced respiratory management (78.4%) compared to all-phase treatment (25.6%, <i>P</i><.0001). There were 17 local recurrences in the treated lesions. Kaplan-Meier analyses showed that there were no differences with regard to mean time to local failure (91.5 vs 98.8 months, <i>P</i>=0.56), mean time to any failure (73.2 vs 78.7 months, <i>P</i>=0.73), or median overall survival (43.3 vs 45.5 months, <i>P</i>=0.56) between patients who underwent advanced respiratory motion management and all-phase treatment.</p><p><strong>Conclusion: </strong>SBRT with advanced respiratory management (the majority with respiratory gating) showed similar efficacy to all-phase treatment approach for stage I NSCLC.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"9 ","pages":"103-110"},"PeriodicalIF":3.6,"publicationDate":"2018-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S175168","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36707193","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":"Silicosis and lung cancer: current perspectives.","authors":"Takashi Sato,&nbsp;Takeshi Shimosato,&nbsp;Dennis M Klinman","doi":"10.2147/LCTT.S156376","DOIUrl":"https://doi.org/10.2147/LCTT.S156376","url":null,"abstract":"<p><p>\"Silica\" refers to crystalline particles formed by the combination of silicon with oxygen. Inhalation of silica particles promotes the development of pulmonary fibrosis that over prolonged periods increases the risk of lung cancer. The International Agency for Research on Cancer (IARC) classified crystalline silica as a human carcinogen in 1997. This categorization was questioned due to 1) the absence of dose-response findings, 2) the presence of confounding variables that complicated interpretation of the data and 3) potential selection bias for compensated silicosis. Yet, recent epidemiologic studies strongly support the conclusion that silica exposure increases the risk of lung cancer in humans independent of confounding factors including cigarette smoke. Based on this evidence, the US Occupational Safety and Health Administration (OSHA) lowered the occupational exposure limit for crystalline silica from 0.1 to 0.05 mg/m³ in 2013. Further supporting the human epidemiologic data, murine models show that chronic silicosis is associated with an increased risk of lung cancer. In animals, the initial inflammation induced by silica exposure is followed by the development of an immunosuppressive microenvironment that supports the growth of lung tumors. This work will review our current knowledge of silica-associated lung cancers, highlighting how recent mechanistic insights support the use of cutting-edge approaches to diagnose and treat silica-related lung cancer.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"9 ","pages":"91-101"},"PeriodicalIF":3.6,"publicationDate":"2018-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S156376","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36737239","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":"Non-small cell to small cell lung cancer on PD-1 inhibitors: two cases on potential histologic transformation.","authors":"Nadine Abdallah,&nbsp;Misako Nagasaka,&nbsp;Eman Abdulfatah,&nbsp;Dongping Shi,&nbsp;Antoinette J Wozniak,&nbsp;Ammar Sukari","doi":"10.2147/LCTT.S173724","DOIUrl":"https://doi.org/10.2147/LCTT.S173724","url":null,"abstract":"<p><strong>Introduction: </strong>Histologic transformation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) is a well-recognized mechanism of resistance in <i>EGFR</i>-mutant adenocarcinoma upon treatment with TKIs, but rarely reported with programmed death1 (PD-1) inhibitors. We report two cases of potential transformation during treatment with PD-1 inhibitors.</p><p><strong>Case presentations: </strong>Case 1, a 65-year-old man was diagnosed with stage IVa lung adenocarcinoma on pleural fluid cytology. He received six cycles of carboplatin and pemetrexed, then maintained on pemetrexed. He had disease progression after nine cycles of pemetrexed and was switched to nivolumab. He progressed after five cycles of nivolumab. Core biopsy of the lung mass revealed SCLC. Case 2, a 68-year-old man was diagnosed with two primary NSCLCs and underwent resection. He had recurrence after several months and was treated with four cycles of carboplatin, paclitaxel, and pembrolizumab on clinical trial, with partial response. He was continued on pembrolizumab and had disease progression after 30 cycles. Biopsy of the new lesions showed SCLC.</p><p><strong>Discussion: </strong>Histologic transformation from NSCLC to SCLC can be explained by the presence of a common cell precursor. Proposed molecular mechanisms include loss of <i>RB1</i>, <i>TP53</i> mutations, and <i>MYC</i> amplification. The distinction between transformation and mixed histology tumors is challenging, especially when pathologic material used for the initial diagnosis is limited. The possibility of a second metachronous primary lung cancer cannot be excluded in our cases.</p><p><strong>Conclusion: </strong>Histologic transformation with PD-1 inhibitors could be under-recognized. Disease progression should prompt re-biopsy to uncover new histology and change in treatment. Future studies are needed to elucidate mechanisms and predictors of transformation.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"9 ","pages":"85-90"},"PeriodicalIF":3.6,"publicationDate":"2018-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S173724","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36737238","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}