scholarly journals Current perspectives on the use of miRNA as a biomarker for EGFR-targeted therapy for non-small cell lung cancer

2017 ◽  
Vol 71 (0) ◽  
pp. 0-0
Author(s):  
Mateusz Florczuk ◽  
Adam Szpechciński ◽  
Joanna Chorostowska-Wynimko
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Predictive Biomarkers ◽  
Small Cell ◽  
Regulatory Function ◽  
Cancer Tissue ◽  
Small Cell Lung ◽  
Egfr Tkis

Non-small cell lung cancer (NSCLC) is the leading cause of death from cancer in the world. Currently, a large number of research studies are conducted to develop and implement new treatment strategies. Intensive efforts are also made to improve the robustness of modern molecular diagnostics to identify more precisely the specific genetic and epigenetic cancer features (predictive biomarkers) and to adjust the most effective treatment options for individual patients (personalized therapy). The so-called targeted therapy based on using epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is nowadays the most widely chosen form of personalized treatment in advanced NSCLC. Favorable response to treatment with EGFR TKIs depends on the presence of somatic mutations in EGFR gene, detectable in lung cancer tissue. The resistance to EGFR TKIs acquired by most patients during the treatment is the main obstacle in overcome in targeted therapy of NSCLC. At present, epi-/genome of lung cancer is intensively screened using high-throughput techniques (e.g. microarrays, Next-Generation Sequencing) to select novel epi-/genetic biomarkers that could be used as predictors of the targeted treatment outcome, apart from single gene alterations. A better understanding of epigenetic mechanisms regulating either the sensitivity or the resistance of NSCLC cells to EGFR TKIs, through activity of small, non-coding miRNA (microRNA) molecules, may become a breakthrough in targeted therapy of lung cancer. During carcinogenesis, miRNAs exhibit their dual regulatory function: they promote cancer development as oncogenes or act as tumor suppressors. From a clinical point of view, such a dual regulatory function of microRNAs might significantly impact the further development of targeted therapies. Moreover, stable forms of tumor-related miRNA are detected not only in tumor tissue, but also in body fluids of NSCLC patients, particularly in their peripheral blood. This finding provides new options of minimally invasive cancer diagnosis and monitoring of treatment effectiveness over time.

scholarly journals Current Landscape of Non-Small Cell Lung Cancer: Epidemiology, Histological Classification, Targeted Therapies, and Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4705
Author(s):  
Olga Rodak ◽  
Manuel David Peris-Díaz ◽  
Mateusz Olbromski ◽  
Marzenna Podhorska-Okołów ◽  
Piotr Dzięgiel
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
Genetic Mutation ◽  
Small Cell ◽  
Small Cell Lung ◽  
Histopathological Classification

Non-small cell lung cancer (NSCLC) is a subtype of the most frequently diagnosed cancer in the world. Its epidemiology depends not only on tobacco exposition but also air quality. While the global trends in NSCLC incidence have started to decline, we can observe region-dependent differences related to the education and the economic level of the patients. Due to an increasing understanding of NSCLC biology, new diagnostic and therapeutic strategies have been developed, such as the reorganization of histopathological classification or tumor genotyping. Precision medicine is focused on the recognition of a genetic mutation in lung cancer cells called “driver mutation” to provide a variety of specific inhibitors of improperly functioning proteins. A rapidly growing group of approved drugs for targeted therapy in NSCLC currently allows the following mutated proteins to be treated: EGFR family (ERBB-1, ERBB-2), ALK, ROS1, MET, RET, NTRK, and RAF. Nevertheless, one of the most frequent NSCLC molecular sub-types remains without successful treatment: the K-Ras protein. In this review, we discuss the current NSCLC landscape treatment focusing on targeted therapy and immunotherapy, including first- and second-line monotherapies, immune checkpoint inhibitors with chemotherapy treatment, and approved predictive biomarkers.

scholarly journals Pretreatment platelet/lymphocyte ratio (PLR) is a significant predictive marker for EGFR targeted therapy in patients with non-small-cell lung cancer

2019 ◽  
Author(s):  
Kejun Liu ◽  
Weiwei Zhang ◽  
Qinquan Tan ◽  
Guanming Jiang ◽  
Jun Jia
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lymphocyte Ratio ◽  
Platelet Lymphocyte Ratio ◽  
Nsclc Patients ◽  
Egfr Tkis

Abstract Non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) gene mutation is benefited from targeted therapy. There is no other superior predictive factor for targeted therapy except EGFR in the clinical. In this study, we analyzed the effect of pretreatment platelet/lymphocyte ratio (PLR) in NSCLC patients. In the present study, a total of 96 patients with EGFR mutations were included in this study. All patients received EGFR targeted therapy, until disease progression, unacceptable toxicity or other factors. The following evaluation was conducted about 3 days before initial treatment: detailed clinical history, physical examination, radiographic results, pathological diagnosis and laboratory parameters including complete blood cell counts and albumin levels. We found that pretreatment PLR is significantly associated to the PFS of NSCLC patients with EGFR targeted therapy. Patients in the PLR ≥190 group had shorter PFS than those in the PLR <190 group (P= 0.009). Furthermore, the 1-year PFS rate in the PLR ≥190 group were inferior to the low value group (P= 0.016). Multivariate analysis confirmed the role of PLR on predicting the efficacy of targeted therapy for advanced NSCLC. In addition, we found that PLR was also an predictive biomarker for grade 3/4 adverse events of diarrhea. In conclusion, high pretreatment PLR was an independent indicator for predicting a poor PFS for NSCLC patients receiving EGFR-TKIs treatment. Further studies are needed to identify the impact of PLR on results of EGFR-TKIs treatment.

scholarly journals Chemo-immunotherapy as first-line treatment for small-cell lung cancer

2020 ◽  
Vol 12 ◽  
pp. 175883592098036
Author(s):  
Saira Farid ◽  
Stephen V. Liu
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Predictive Biomarkers ◽  
High Response Rate ◽  
Small Cell ◽  
Standards Of Care ◽  
Small Cell Lung ◽  
First Line ◽  
Line Chemotherapy

Small-cell lung cancer (SCLC) is a highly lethal subtype of lung cancer. Despite concerted efforts over the past several decades, there have been limited therapeutic advances. Traditional chemotherapy offers a high response rate and rapid symptomatic improvement, but its benefit is fleeting, and relapse is quick and unforgiving. Immunotherapy has delivered improved outcomes for patients with many cancers and there was compelling rationale for development in SCLC. While initial efforts with cytotoxic T-lymphocyte protein-4 inhibitors failed to improve upon chemotherapy alone, the addition of programmed death ligand-1 (PD-L1) inhibitors to first-line chemotherapy finally provided long-awaited gains in survival. Atezolizumab, when added to carboplatin and etoposide, improved both progression-free survival and overall survival. Durvalumab, when added to platinum plus etoposide, similarly improved OS. Biomarker development has stalled as PD-L1 expression and tumor mutational burden have not been useful predictive biomarkers. However, based on the significant survival improvements, both atezolizumab and durvalumab were approved by the US Food and Drug Administration to be given with first-line chemotherapy, and these regimens represent the new standards of care for SCLC.

scholarly journals Predictive value of pretreatment PD-L1 expression in EGFR-mutant non-small cell lung cancer: a meta-analysis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhiyu Peng ◽  
Huahang Lin ◽  
Ke Zhou ◽  
Senyi Deng ◽  
Jiandong Mei
Keyword(s):  
Lung Cancer ◽  
Sensitivity Analysis ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Predictive Value ◽  
Meta Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Egfr Mutant ◽  
Egfr Tkis

Abstract Objective To investigate the predictive value of programmed death-ligand 1 (PD-L1) expression in non-small cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Methods We conducted a systemic search of PubMed, EMBASE, and the Cochrane Library from 1 January 2000 to 30 August 2020, to identify related studies. We combined the hazard ratio (HR) and 95% confidence interval (CI) to assess the correlation of PD-L1 expression with progression-free survival (PFS) and overall survival (OS). We assessed the quality of the included studies by the Newcastle–Ottawa Scale (NOS). We performed subgroup analyses based on immunohistochemistry (IHC) scoring system, IHC antibodies, sample size, countries, and survival analysis mode. Sensitivity analysis and evaluation of publication bias were also performed. Results Twelve studies including 991 patients met the criteria. The mean NOS score was 7.42 ± 1.19. Patients with high PD-L1 expression was associated with poorer PFS (HR = 1.90; 95% CI = 1.16–3.10; P = 0.011), while there was no association between PD-L1 expression and OS (HR = 1.19; 95% CI = 0.99–1.43; P = 0.070). Subgroup analysis prompted IHC scoring systems, IHC antibodies, and sample size have important effects on heterogeneity. The pooled results were robust according to the sensitivity analysis. Conclusions The result of this meta-analysis suggested that PD-L1 expression might be a predictive biomarker for EGFR-mutant non-small cell lung cancer treated with EGFR-TKIs.

scholarly journals Protein Kinase C as a Therapeutic Target in Non-Small Cell Lung Cancer

2021 ◽  
Vol 22 (11) ◽  
pp. 5527
Author(s):  
Mohammad Mojtaba Sadeghi ◽  
Mohamed F. Salama ◽  
Yusuf A. Hannun
Keyword(s):  
Lung Cancer ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Predictive Biomarkers ◽  
Small Cell ◽  
Small Cell Lung ◽  
Kinase C ◽  
Pkc Isozymes

Driver-directed therapeutics have revolutionized cancer treatment, presenting similar or better efficacy compared to traditional chemotherapy and substantially improving quality of life. Despite significant advances, targeted therapy is greatly limited by resistance acquisition, which emerges in nearly all patients receiving treatment. As a result, identifying the molecular modulators of resistance is of great interest. Recent work has implicated protein kinase C (PKC) isozymes as mediators of drug resistance in non-small cell lung cancer (NSCLC). Importantly, previous findings on PKC have implicated this family of enzymes in both tumor-promotive and tumor-suppressive biology in various tissues. Here, we review the biological role of PKC isozymes in NSCLC through extensive analysis of cell-line-based studies to better understand the rationale for PKC inhibition. PKC isoforms α, ε, η, ι, ζ upregulation has been reported in lung cancer, and overexpression correlates with worse prognosis in NSCLC patients. Most importantly, PKC isozymes have been established as mediators of resistance to tyrosine kinase inhibitors in NSCLC. Unfortunately, however, PKC-directed therapeutics have yielded unsatisfactory results, likely due to a lack of specific evaluation for PKC. To achieve satisfactory results in clinical trials, predictive biomarkers of PKC activity must be established and screened for prior to patient enrollment. Furthermore, tandem inhibition of PKC and molecular drivers may be a potential therapeutic strategy to prevent the emergence of resistance in NSCLC.

scholarly journals RNA-Based Assay for Next-Generation Sequencing of Clinically Relevant Gene Fusions in Non-Small Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 139
Author(s):  
Caterina De Luca ◽  
Francesco Pepe ◽  
Antonino Iaccarino ◽  
Pasquale Pisapia ◽  
Luisella Righi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Limit Of Detection ◽  
Predictive Biomarkers ◽  
Small Cell ◽  
Clinical Samples ◽  
Gene Fusions ◽  
Small Cell Lung ◽  
Relevant Gene

Gene fusions represent novel predictive biomarkers for advanced non-small cell lung cancer (NSCLC). In this study, we validated a narrow NGS gene panel able to cover therapeutically-relevant gene fusions and splicing events in advanced-stage NSCLC patients. To this aim, we first assessed minimal complementary DNA (cDNA) input and the limit of detection (LoD) in different cell lines. Then, to evaluate the feasibility of applying our panel to routine clinical samples, we retrospectively selected archived lung adenocarcinoma histological and cytological (cell blocks) samples. Overall, our SiRe RNA fusion panel was able to detect all fusions and a splicing event harbored in a RNA pool diluted up to 2 ng/µL. It also successfully analyzed 46 (95.8%) out of 48 samples. Among these, 43 (93.5%) out of 46 samples reproduced the same results as those obtained with conventional techniques. Intriguingly, the three discordant results were confirmed by a CE-IVD automated real-time polymerase chain reaction (RT-PCR) analysis (Easy PGX platform, Diatech Pharmacogenetics, Jesi, Italy). Based on these findings, we conclude that our new SiRe RNA fusion panel is a valid and robust tool for the detection of clinically relevant gene fusions and splicing events in advanced NSCLC.

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