Lung Cancer: Targets and Therapy最新文献_第3页

Polo-like kinase 1 inhibition in NSCLC: mechanism of action and emerging predictive biomarkers polo样激酶1在非小细胞肺癌中的抑制:作用机制和新兴的预测性生物标志物

IF 3.6

Lung Cancer: Targets and Therapy Pub Date : 2019-07-01 DOI: 10.2147/LCTT.S177618

J. Stratmann, M. Sebastian

{"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}

引用次数: 11

Impact of smoking on frequency and spectrum of K-RAS and EGFR mutations in treatment naive Indonesian lung cancer patients 吸烟对印尼初治肺癌患者K-RAS和EGFR突变频率和谱的影响

IF 3.6

Lung Cancer: Targets and Therapy Pub Date : 2019-06-17 DOI: 10.2147/LCTT.S180692

N. Masykura, J. Zaini, E. Syahruddin, S. Andarini, A. Hudoyo, Refniwita Yasril, A. Ridwanuloh, Heriawaty Hidajat, F. Nurwidya, A. Utomo

{"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}

引用次数: 7

Driver oncogenes in Sub-Saharan African patients with non-small cell lung cancer 撒哈拉以南非洲非小细胞肺癌患者的驱动癌基因

IF 3.6

Lung Cancer: Targets and Therapy Pub Date : 2016-11-30 DOI: 10.2147/LCTT.S116762

B. Legius, S. van den Broecke, I. Muylle, V. Ninane

引用次数: 3

Lung cancer in Brazil: epidemiology and treatment challenges 巴西的肺癌:流行病学和治疗挑战

IF 3.6

Lung Cancer: Targets and Therapy Pub Date : 2016-11-14 DOI: 10.2147/LCTT.S93604

V. D. de Sá, J. Coelho, V. Capelozzi, Sergio Jobim de Azevedo

{"title":"Lung cancer in Brazil: epidemiology and treatment challenges","authors":"V. D. de Sá, J. Coelho, V. Capelozzi, Sergio Jobim de Azevedo","doi":"10.2147/LCTT.S93604","DOIUrl":"https://doi.org/10.2147/LCTT.S93604","url":null,"abstract":"Lung cancer persists throughout the world as a major cause of death. In 2014, data from the Brazilian National Cancer Institute (INCA) estimated 16.400 new cases of lung cancer among men (second most common) and 10.930 new cases among women (fourth most common). These data are consistent for all Brazilian regions and reflect the trends of cancer in the country over the last decade. Brazil is a continental country, the largest in Latin America and fifth in the world, with an estimated population of >200 million. Although the discrepancy in the national income between rich and poor has diminished in the last 2 decades, it is still huge. More than 75% of the Brazilian population do not have private health insurance and rely on the national health care system, where differences in standard of cancer care are evident. It is possible to point out differences from the recommendations of international guidelines in every step of the lung cancer care, from the diagnosis to the treatment of advanced disease. This review aims to describe and recognize these differences as a way to offer a real discussion for future modifications and action points toward delivery of better oncology care in our country.","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"28 1","pages":"141 - 148"},"PeriodicalIF":3.6,"publicationDate":"2016-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80244767","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}

引用次数: 25

Oligometastatic non-small-cell lung cancer: current treatment strategies 少转移性非小细胞肺癌:目前的治疗策略

IF 3.6

Lung Cancer: Targets and Therapy Pub Date : 2016-11-04 DOI: 10.2147/LCTT.S101639

P. Richard, R. Rengan

{"title":"Oligometastatic non-small-cell lung cancer: current treatment strategies","authors":"P. Richard, R. Rengan","doi":"10.2147/LCTT.S101639","DOIUrl":"https://doi.org/10.2147/LCTT.S101639","url":null,"abstract":"The oligometastatic disease theory was initially described in 1995 by Heilman and Weichselbaum. Since then, much work has been performed to investigate its existence in many solid tumors. This has led to subclassifications of stage IV cancer, which could redefine our treatment approaches and the therapeutic outcomes for this historically “incurable” entity. With a high incidence of stage IV disease, non-small-cell lung cancer (NSCLC) remains a difficult cancer to treat and cure. Recent work has proven the existence of an oligometastatic state in NSCLC in terms of properly selecting patients who may benefit from aggressive therapy and experience long-term overall survival. This review discusses the current treatment approaches used in oligometastatic NSCLC and provides the evidence and rationale for each approach. The prognostic factors of many trials are discussed, which can be used to properly select patients for aggressive treatment regimens. Future advances in both molecular profiling of NSCLC to find targetable mutations and investigating patient selection may increase the number of patients diagnosed with oligometastatic NSCLC. As this disease entity increases, it is of utmost importance for oncologists treating NSCLC to be aware of the current treatment strategies that exist and the potential advantages/disadvantages of each.","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"84 1","pages":"129 - 140"},"PeriodicalIF":3.6,"publicationDate":"2016-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80874625","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}

引用次数: 23

Radiation-induced esophagitis in lung cancer 肺癌放射性食管炎

IF 3.6

Lung Cancer: Targets and Therapy Pub Date : 2016-10-13 DOI: 10.2147/LCTT.S96443

S. Baker, A. Fairchild

引用次数: 51

Electromagnetic navigation bronchoscopy: clinical utility in the diagnosis of lung cancer 电磁导航支气管镜在肺癌诊断中的临床应用

IF 3.6

Lung Cancer: Targets and Therapy Pub Date : 2016-10-12 DOI: 10.2147/LCTT.S98643

L. Seijo

引用次数: 13

Spotlight on crizotinib in the first-line treatment of ALK-positive advanced non-small-cell lung cancer: patients selection and perspectives 聚焦克唑替尼一线治疗alk阳性晚期非小细胞肺癌:患者选择和观点

IF 3.6

Lung Cancer: Targets and Therapy Pub Date : 2016-06-17 DOI: 10.2147/LCTT.S99303

E. G. Leprieur, V. Fallet, J. Cadranel, M. Wislez

{"title":"Spotlight on crizotinib in the first-line treatment of ALK-positive advanced non-small-cell lung cancer: patients selection and perspectives","authors":"E. G. Leprieur, V. Fallet, J. Cadranel, M. Wislez","doi":"10.2147/LCTT.S99303","DOIUrl":"https://doi.org/10.2147/LCTT.S99303","url":null,"abstract":"Around 4% of advanced non-small-cell lung cancers (NSCLCs) have an ALK rearrangement at the time of diagnosis. This molecular feature is more frequent in young patients, with no/light smoking habit and with adenocarcinoma pathological subtype. Crizotinib is a tyrosine kinase inhibitor, targeting ALK, ROS1, RON, and MET. The preclinical efficacy results led to a fast-track clinical development. The US Food and Drug Administration (FDA) approval was achieved after the Phase I clinical trial in 2011 in ALK-rearranged advanced NSCLC progressing after a first-line treatment. In 2013, the randomized Phase III trial PROFILE-1007 confirmed the efficacy of crizotinib in ALK-rearranged NSCLC, compared to cytotoxic chemotherapy, in second-line setting or more. In 2014, the PROFILE-1014 trial showed the superiority of crizotinib in the first-line setting compared to the pemetrexed platinum doublet chemotherapy. The response rate was 74%, and the progression-free survival was 10.9 months with crizotinib. Based on these results, crizotinib received approval from the FDA and European Medicines Agency for first-line treatment of ALK-rearranged NSCLC. The various molecular mechanisms at the time of the progression (ALK mutations or amplification, ALK-independent mechanisms) encourage performing re-biopsy at the time of progression under crizotinib. The best treatment strategy at the progression (crizotinib continuation beyond progression, switch to second-generation tyrosine kinase inhibitors, or cytotoxic chemotherapy) depends on the phenotype of the progression, the molecular status, and the physical condition of the patient.","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"73 1","pages":"83 - 90"},"PeriodicalIF":3.6,"publicationDate":"2016-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85649449","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}

引用次数: 14

Profile of rociletinib and its potential in the treatment of non-small-cell lung cancer 罗西莱替尼的概况及其治疗非小细胞肺癌的潜力

IF 3.6

Lung Cancer: Targets and Therapy Pub Date : 2016-05-18 DOI: 10.2147/LCTT.S94337

P. Tran, S. Klempner

{"title":"Profile of rociletinib and its potential in the treatment of non-small-cell lung cancer","authors":"P. Tran, S. Klempner","doi":"10.2147/LCTT.S94337","DOIUrl":"https://doi.org/10.2147/LCTT.S94337","url":null,"abstract":"Patients with non-small-cell lung cancer (NSCLC) harboring activating mutations in EGFR benefit from treatment with EGFR small-molecule tyrosine-kinase inhibitors. However, the development of acquired resistance to EGFR inhibitors is universal and limits treatment efficacy. Over half of patients receiving first-generation EGFR inhibitors (erlotinib and gefitinib) develop resistance via the gatekeeper EGFR T790M (EGFRT790M) mutation, and therapies able to overcome T790M-mediated resistance have been an unmet need in NSCLC. Rociletinib (CO-1686) is a third-generation small-molecule EGFR inhibitor with potent activity against EGFRT790M currently in advanced clinical development in NSCLC. Early clinical data suggested significant activity in EGFR-mutant NSCLC harboring T790M alterations. However, important questions regarding side-effect profile, comparability to competitor compounds, acquired resistance, EGFR-therapy sequencing, and combination therapies remain. Here, we review the available preclinical and clinical data for rociletinib, highlight the comparison to other third-generation EGFR inhibitors, and discuss resistance implications and future directions in NSCLC.","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":"86 1","pages":"91 - 97"},"PeriodicalIF":3.6,"publicationDate":"2016-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77633583","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}

引用次数: 11

Modern management of malignant pleural mesothelioma 恶性胸膜间皮瘤的现代治疗

IF 3.6

Lung Cancer: Targets and Therapy Pub Date : 2016-05-03 DOI: 10.2147/LCTT.S83338

Shivani Patel, J. Dowell

引用次数: 32