Lung Cancer: Targets and Therapy最新文献

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Immune Checkpoint Inhibitors for the Treatment of Unresectable Stage III Non-Small Cell Lung Cancer: Emerging Mechanisms and Perspectives. 免疫检查点抑制剂治疗不可切除的III期非小细胞肺癌:新兴机制和观点。
IF 3.6
Lung Cancer: Targets and Therapy Pub Date : 2019-12-31 eCollection Date: 2019-01-01 DOI: 10.2147/LCTT.S184380
Hiroyuki Inoue, Isamu Okamoto
{"title":"Immune Checkpoint Inhibitors for the Treatment of Unresectable Stage III Non-Small Cell Lung Cancer: Emerging Mechanisms and Perspectives.","authors":"Hiroyuki Inoue,&nbsp;Isamu Okamoto","doi":"10.2147/LCTT.S184380","DOIUrl":"https://doi.org/10.2147/LCTT.S184380","url":null,"abstract":"<p><p>There has been no improvement in outcome for patients with unresectable locally advanced (stage III) non-small cell lung cancer (NSCLC) for more than 10 years. The standard treatment for these patients is definitive concurrent chemotherapy and radiation (CCRT). Although the goal of treatment in this setting is to achieve a cure, most patients progress and their prognosis is poor, with a 5-year survival rate of 15-30%. There is thus an urgent need for the development of novel anticancer treatments in this patient population. Recent advances in cancer immunotherapy have led to a marked improvement in clinical outcome for advanced NSCLC. Such immunotherapy mainly consists of the administration of immune checkpoint inhibitors (ICIs) such as antibodies to cytotoxic T lymphocyte-associated protein-4 (CTLA-4) or to either programmed cell death-1 (PD-1) or its ligand PD-L1. Durvalumab (MEDI4736) is a high-affinity human immunoglobulin G1 monoclonal antibody that blocks the binding of PD-L1 on tumor cells or antigen-presenting cells to PD-1 on T cells. The PACIFIC study recently evaluated consolidation immunotherapy with durvalumab versus placebo administered after concurrent chemoradiotherapy (CCRT) in patients with unresectable stage III NSCLC. It revealed a significant improvement in both progression-free and overall survival with durvalumab, and this improvement was associated with a favorable safety profile. This achievement has made durvalumab a standard of care for consolidation after CCRT in patients with unresectable stage III NSCLC, and it has now been approved in this setting by regulatory agencies in the United States, Canada, Japan, Australia, Switzerland, Malaysia, Singapore, India, and the United Arab Emirates. In this review, we briefly summarize the results of the PACIFIC trial, including those of post hoc analysis, and we address possible molecular mechanisms, perspectives, and remaining questions related to combined treatment with CCRT and ICIs in this patient population.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2019-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S184380","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37677185","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}
引用次数: 9
Outcomes Following Stereotactic Body Radiotherapy with Intensity-Modulated Therapy versus Three-Dimensional Conformal Radiotherapy in Early Stage Non-Small Cell Lung Cancer. 立体定向体放疗加调强治疗与三维适形放疗治疗早期非小细胞肺癌的疗效比较。
IF 3.6
Lung Cancer: Targets and Therapy Pub Date : 2019-12-20 eCollection Date: 2019-01-01 DOI: 10.2147/LCTT.S235713
Michael Mix, Sean Tanny, Tamara Nsouli, Ryan Alden, Rishabh Chaudhari, Russell Kincaid, Paula F Rosenbaum, Jeffrey A Bogart, Paul Aridgides
{"title":"Outcomes Following Stereotactic Body Radiotherapy with Intensity-Modulated Therapy versus Three-Dimensional Conformal Radiotherapy in Early Stage Non-Small Cell Lung Cancer.","authors":"Michael Mix,&nbsp;Sean Tanny,&nbsp;Tamara Nsouli,&nbsp;Ryan Alden,&nbsp;Rishabh Chaudhari,&nbsp;Russell Kincaid,&nbsp;Paula F Rosenbaum,&nbsp;Jeffrey A Bogart,&nbsp;Paul Aridgides","doi":"10.2147/LCTT.S235713","DOIUrl":"https://doi.org/10.2147/LCTT.S235713","url":null,"abstract":"<p><strong>Introduction: </strong>The treatment techniques used for stereotactic body radiation therapy (SBRT) for early-stage lung cancer continue to evolve. In this study, clinical outcomes following SBRT were evaluated according to the use of either 3D conformal radiotherapy (3DCRT) or intensity-modulated radiation therapy (IMRT).</p><p><strong>Patients and methods: </strong>Patients with stage I NSCLC who received SBRT from 2007 to 2015 were retrospectively reviewed. Disease control and survival were assessed using Kaplan-Meier estimates. Dosimetric analyses for target dose heterogeneity and coverage were performed.</p><p><strong>Results: </strong>A total of 297 patients with 351 lesions were included. 3DCRT was used in 52% and IMRT in 48%. IMRT was utilized at a higher rate in more recent years. The most common regimens were 48 Gy in 4 fractions and 54-60 Gy in 3 fractions. With a median follow up of 22.7 months, there were 17 local failures for a crude relapse rate of 5.7%. Local failure did not differ in patients treated with 3DCRT and IMRT (4.9% vs 6.5%, p=0.573). Mean dose to gross tumor volume (GTV) as a percent of prescription dose was higher with 3DCRT compared with IMRT (107.7% vs 103.6%, p < 0.0001). Tumor stage, histology, and SBRT regimen did not correlate with local tumor control. Overall survival for the entire population approximated 72% at 2 years. Treatment was well tolerated with 6 documented grade 3+ events.</p><p><strong>Conclusion: </strong>In this single-institution cohort of SBRT for early-stage NSCLC, there was no discernible difference in clinical outcomes between those treated with 3DCRT and IMRT.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2019-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S235713","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37518232","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}
引用次数: 3
Approaches to Tumor Classification in Pulmonary Sarcomatoid Carcinoma. 肺肉瘤样癌肿瘤分型的探讨。
IF 3.6
Lung Cancer: Targets and Therapy Pub Date : 2019-12-05 eCollection Date: 2019-01-01 DOI: 10.2147/LCTT.S186779
Chiara Baldovini, Giulio Rossi, Alessia Ciarrocchi
{"title":"Approaches to Tumor Classification in Pulmonary Sarcomatoid Carcinoma.","authors":"Chiara Baldovini,&nbsp;Giulio Rossi,&nbsp;Alessia Ciarrocchi","doi":"10.2147/LCTT.S186779","DOIUrl":"https://doi.org/10.2147/LCTT.S186779","url":null,"abstract":"<p><p>Pulmonary sarcomatoid carcinoma (PSC) is a heterogeneous category of primary lung cancer accounting from 0.3% to 3% of all primary lung malignancies. According to the most recent 2015 World Health Organization (WHO) classification, PSC includes several different variants of malignant epithelial tumors (carcinomas) histologically mimicking sarcomas showing or entirely lacking a conventional component of non-small cell lung cancer (NSCLC). Thus, this rare subheading of lung neoplasms includes pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, pulmonary blastoma, and carcinosarcoma. A diagnosis of PSC may be suspected on small biopsy or cytology, but commonly requires a surgical resection to reach a conclusive definition. The majority of patients with PSC consists of elderly, smoking men with a large, peripheral mass characterized by well-defined margins. However, presentation with a central, polypoid endobronchial lesion is well-documented, particularly in pleomorphic carcinoma and carcinosarcoma showing a squamous cell carcinoma component. As expected, PSC may pose diagnostic problems and immunohistochemistry is largely used when pathologists deal these tumors in routine practice. Indeed, PSC tends to overexpress molecules associated with the epithelial-to-mesenchymal transition, such as vimentin, but the panel of immunostains also includes epithelial markers (cytokeratins, EMA), TTF-1, p40 and negative markers (e.g., melanocytic, mesothelial and sarcoma-related primary antibodies). Although rare, PSC has increased their interest among oncologist community for different reasons: a. identification of the epithelial-to-mesenchymal phenomenon as a major mechanism of secondary resistance to tyrosine kinase inhibitors; b. over-expression of PD-L1 and effective treatment with immunotherapy; c. identification of <i>c-MET</i> exon 14 skipping mutation representing an effective target to crizotinib and other specific inhibitors. In this review, the feasibility of the diagnosis of PSC, its differential diagnosis and novel molecular findings characterizing this group of lung tumor are discussed.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2019-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S186779","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37446465","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}
引用次数: 38
Time To Response In Patients With Advanced Anaplastic Lymphoma Kinase (ALK)-Positive Non-Small-Cell Lung Cancer (NSCLC) Receiving Alectinib In The Phase II NP28673 And NP28761 Studies. 在 NP28673 和 NP28761 II 期研究中接受阿来替尼治疗的晚期无性淋巴瘤激酶 (ALK) 阳性非小细胞肺癌 (NSCLC) 患者的应答时间。
IF 5.1
Lung Cancer: Targets and Therapy Pub Date : 2019-11-13 eCollection Date: 2019-01-01 DOI: 10.2147/LCTT.S209231
Shirish Gadgeel, Alice T Shaw, Fabrice Barlesi, Lucio Crino, James Ch Yang, Anne-Marie Dingemans, Dong-Wan Kim, Filippo de Marinis, Mathias Schulz, Shiyao Liu, Ravindra Gupta, Vlatka Smoljanovic, Sai-Hong Ignatius Ou
{"title":"Time To Response In Patients With Advanced Anaplastic Lymphoma Kinase (<i>ALK</i>)-Positive Non-Small-Cell Lung Cancer (NSCLC) Receiving Alectinib In The Phase II NP28673 And NP28761 Studies.","authors":"Shirish Gadgeel, Alice T Shaw, Fabrice Barlesi, Lucio Crino, James Ch Yang, Anne-Marie Dingemans, Dong-Wan Kim, Filippo de Marinis, Mathias Schulz, Shiyao Liu, Ravindra Gupta, Vlatka Smoljanovic, Sai-Hong Ignatius Ou","doi":"10.2147/LCTT.S209231","DOIUrl":"10.2147/LCTT.S209231","url":null,"abstract":"<p><strong>Introduction: </strong>Alectinib is a highly selective and potent ALK inhibitor, approved for the treatment of patients with metastatic <i>ALK</i>+ NSCLC based on results from the Phase II global NP28673 (NCT01801111) and North American NP28761 (NCT01871805) studies.</p><p><strong>Methods: </strong>This exploratory analysis of two Phase II studies of alectinib (NP28673/NP28761) investigated time to systemic response (TTR) and time to central nervous system (CNS) response (TTCR) in patients with previously treated advanced anaplastic lymphoma kinase fusion gene-positive (<i>ALK</i>+) non-small-cell lung cancer. Patients (n=225) received 600 mg oral alectinib twice daily and had scans every 6/8 weeks (NP28673/NP28761).</p><p><strong>Results: </strong>For NP28673 and NP28761, respectively: median follow-up was 21.3 months/17.0 months; most responders (72.6%/82.9%) responded by the first disease assessment; median TTR was 8 weeks (95% confidence interval [CI]: 8.00-8.14)/6 weeks (95% CI: 5.86-6.14); median TTCR in responders with measurable baseline CNS disease was 8 weeks (95% CI: 7.86-10.29)/6 weeks (95% CI: 5.71-not evaluable). Similar results were observed regardless of measurable/non-measurable disease.</p><p><strong>Discussion: </strong>These data suggest that alectinib achieves a rapid response in patients, both systemically and in the CNS.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2019-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/06/2a/lctt-10-125.PMC6859466.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37602775","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}
引用次数: 0
Landscape on CT screening for lung cancer in Asia. 亚洲癌症CT筛查的前景。
IF 3.6
Lung Cancer: Targets and Therapy Pub Date : 2019-09-30 eCollection Date: 2019-01-01 DOI: 10.2147/LCTT.S192643
Natthaya Triphuridet, Claudia Henschke
{"title":"Landscape on CT screening for lung cancer in Asia.","authors":"Natthaya Triphuridet,&nbsp;Claudia Henschke","doi":"10.2147/LCTT.S192643","DOIUrl":"https://doi.org/10.2147/LCTT.S192643","url":null,"abstract":"<p><p>Lung cancer remains the leading cause of cancer incidence and mortality worldwide. Approximately 60% of the world's new cases of lung cancer and deaths from it are expected in Asia in 2018. Currently, lung cancer screening using low-dose computed tomography (LDCT) is recommended for heavy smokers in North America, Europe and some countries in Asia. Tobacco smoking being the major risk factor for lung cancer, but in Asia, lung cancer in never-smokers (LCINS) is also a concern. This paper reviews on lung cancer incidence, mortality, etiology, smoking in Asia, and systematic reviews on LDCT lung cancer screening studies, including ongoing projects and recommendation on lung cancer screening in Asia. Some of the earliest studies of LDCT lung cancer screening worldwide were in Asia. Many countries in Asia have developed LDCT screening studies in various high-risk participants. Currently, there are several ongoing large-scale lung cancer screening trials to evaluate the efficacy of LDCT screening for never-smokers and light smokers, as well as heavy smokers, and to evaluate the feasibility of population-based LDCT lung cancer screening.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2019-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S192643","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41222406","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}
引用次数: 23
A retrospective study evaluating the pretreatment tumor volume (PTV) in non-small cell lung cancer (NSCLC) as a predictor of response to program death-1 (PD-1) inhibitors 一项评估非小细胞肺癌(NSCLC)预处理肿瘤体积(PTV)作为对程序性死亡-1 (PD-1)抑制剂反应的预测因子的回顾性研究
IF 3.6
Lung Cancer: Targets and Therapy Pub Date : 2019-09-12 DOI: 10.2147/LCTT.S219886
M. Nagasaka, Nadine H Abdallah, Marcus Crosby, Nithin Thummala, Dhaval Patel, A. Wozniak, S. Gadgeel, J. Abrams, A. Sukari
{"title":"A retrospective study evaluating the pretreatment tumor volume (PTV) in non-small cell lung cancer (NSCLC) as a predictor of response to program death-1 (PD-1) inhibitors","authors":"M. Nagasaka, Nadine H Abdallah, Marcus Crosby, Nithin Thummala, Dhaval Patel, A. Wozniak, S. Gadgeel, J. Abrams, A. Sukari","doi":"10.2147/LCTT.S219886","DOIUrl":"https://doi.org/10.2147/LCTT.S219886","url":null,"abstract":"Introduction of hypothesis Little information is available regarding the imaging characteristics that assist in differentiating responders from non-responders. We hypothesized that patients with higher pretreatment tumor volume (PTV) would have lower response rates and shorter overall survival (OS). Methods Data from patients who received at least one dose of program death-1 (PD-1) inhibitors before August 31, 2016 were captured from our institution’s pharmacy database. The primary objective was to determine the association of PTV with best response, evaluated utilizing RECIST v1.1 criteria. Secondary objectives were estimation of progression-free survival (PFS) and OS. PTV was measured using the Philips Intellispace Multi-Modality Tumor Tracking application. Results 116 non-small cell lung cancer (NSCLC) patients were evaluated. 66% patients had adenocarcinoma, 28% had squamous cell carcinoma and 5% had poorly differentiated NSCLC. Median PTV was 53.7 cm3 (95% CI: 13.3–107.9). Only one individual had no metastases and the remainder had M1 disease; 38% M1a, 10% M1b, 51% M1c. Most (79%) were previously treated. There were no complete responses; among those followed for at least 6 weeks, 26% had a partial response, 39% stable disease and 34% PD; 4% had no recorded response. There were no strong associations of PTV with any of the demographic or clinical characteristics. There was no association between PTV and OS (HR 1.2, P=0.26) or PFS (HR 1.1, P=0.47). Liver metastasis was associated with shorter survival (HR=2.8, P=0.05). Conclusion PTV in NSCLC did not prove to be a predictor of response to PD-1 inhibitors but having liver metastasis was associated with significantly shorter survival.","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2019-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87017111","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: 4
Profile of entrectinib and its potential in the treatment of ROS1-positive NSCLC: evidence to date. 恩曲替尼的概况及其在治疗ROS1阳性NSCLC中的潜力:迄今为止的证据。
IF 3.6
Lung Cancer: Targets and Therapy Pub Date : 2019-09-09 eCollection Date: 2019-01-01 DOI: 10.2147/LCTT.S190786
Francesco Facchinetti, Luc Friboulet
{"title":"Profile of entrectinib and its potential in the treatment of ROS1-positive NSCLC: evidence to date.","authors":"Francesco Facchinetti,&nbsp;Luc Friboulet","doi":"10.2147/LCTT.S190786","DOIUrl":"https://doi.org/10.2147/LCTT.S190786","url":null,"abstract":"<p><p>ROS1 inhibition provides impressive survival benefits in <i>ROS1</i>-rearranged non-small cell lung cancer (NSCLC) patients. Crizotinib is the only tyrosine kinase inhibitor (TKI) approved by both FDA and EMA for the treatment of ROS1-positive lung cancer. In addition, several TKI have been tested with preliminary proofs of success in this oncogene-driven disease, either in the post-crizotinib setting or as first-line targeted agents. Here we present the evidence concerning entrectinib, an ALK/ROS1/NTRK inhibitor developed across different tumor types harboring rearrangements in these genes, in the context of ROS1-driven NSCLC. Of interest, in August 2019 entrectinib was granted by FDA accelerated approval for the treatment of <i>ROS1</i>-rearranged NSCLC, as well as of NTRK-driven solid tumors.</p>","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2019-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/LCTT.S190786","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41222327","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}
引用次数: 14
TKI-resistant ALK-rearranged lung adenocarcinoma with secondary CTNNB1 p.S45V and tertiary ALK p.I1171N mutations tki耐药ALK重排肺腺癌伴继发性CTNNB1 p.S45V和继发性ALK p.I1171N突变
IF 3.6
Lung Cancer: Targets and Therapy Pub Date : 2019-08-01 DOI: 10.2147/LCTT.S212406
Madhu M Ouseph, A. Taber, H. Khurshid, R. Madison, B. Aswad, M. Resnick, E. Yakirevich, Siraj M. Ali, Nimesh R. Patel
{"title":"TKI-resistant ALK-rearranged lung adenocarcinoma with secondary CTNNB1 p.S45V and tertiary ALK p.I1171N mutations","authors":"Madhu M Ouseph, A. Taber, H. Khurshid, R. Madison, B. Aswad, M. Resnick, E. Yakirevich, Siraj M. Ali, Nimesh R. Patel","doi":"10.2147/LCTT.S212406","DOIUrl":"https://doi.org/10.2147/LCTT.S212406","url":null,"abstract":"Abstract Anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) is an important molecular subgroup of tumors that are typically sensitive to tyrosine kinase inhibitors (TKIs). Although a substantial portion of patients benefit from TKIs, this approach is complicated by intrinsic and acquired resistance. We report a patient with ALK-rearranged NSCLC who showed an initial response to targeted therapy, but developed resistance to multiple TKIs. Serial comprehensive genomic profiling (CGP) was performed at four independent points during the clinical course. We review the pathology and clonal progression of the tumor, with CGP identifying a secondary CTNNB1 p.S45V mutation after the initiation of targeted therapy, followed by tertiary ALK p.I1171N. The presence of an alteration in a second oncogenic driver gene suggests a possible mechanism for resistance, and a secondary therapeutic target. Due to the involvement of Wnt signaling in the pathogenesis of many tumors and its association with immune evasion, a variety of therapeutic strategies are being developed to target this pathway. This case exemplifies the challenges of targeted therapeutics in the face of tumor progression, as well as the increasing role of genomics in understanding tumor biology.","PeriodicalId":18066,"journal":{"name":"Lung Cancer: Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82631053","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: 1
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":null,"pages":null},"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":null,"pages":null},"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
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