Sequencing Therapy for Genetically Defined Subgroups of Non–Small Cell Lung Cancer

2018 ◽  
pp. 726-739 ◽  
Author(s):  
Helena A. Yu ◽  
David Planchard ◽  
Christine M. Lovly
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Small Molecule ◽  
Cell Lung Cancer ◽  
Small Molecule Inhibitors ◽  
Small Cell ◽  
Driver Mutations ◽  
Tyrosine Kinase Receptor ◽  
Small Cell Lung ◽  
Anaplastic Lymphoma

The practice of precision medicine for patients with metastatic non–small cell lung cancer (NSCLC), particularly those patients with adenocarcinoma histology (the predominant subtype of NSCLC), has become the accepted standard of care worldwide. Implementation of prospective tumor molecular profiling and rational therapeutic decision-making based on the presence of recurrently detected oncogenic “driver” alterations in the tumor genome has revolutionized the way that lung cancer is diagnosed and treated in the clinic. Over the past two decades, there has been a deluge of therapeutically actionable driver alterations and accompanying small molecule inhibitors to target these drivers. Herein, we synthesize a large and rapidly growing body of literature regarding therapeutic inhibition of driver mutations. We focus on established targets, including EGFR, anaplastic lymphoma kinase (ALK), ROS1, BRAF, RET, MET, HER2, and neurotrophic tyrosine kinase receptor (NTRK), with a particular emphasis on the sequencing of small molecule inhibitors in these genetically defined cohorts of patients with lung cancer.

Abstract LB-232: Potent, novel small molecule inhibitors targeting EGFR L858R/T790M mutation for non-small cell lung cancer

2014 ◽  
Author(s):  
Dhanalakshmi Sivanandhan ◽  
Payal K. Parikh ◽  
Avinash Sheshachalam ◽  
Chandregowda V ◽  
Rajagopal Bhakthavatchalam ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Small Molecule ◽  
Cell Lung Cancer ◽  
Small Molecule Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
T790m Mutation

scholarly journals The development of potential targets in the treatment of non-small cell lung cancer

2016 ◽  
Vol 11 (1) ◽  
pp. 225-231
Author(s):  
Jimin Zhang ◽  
Zhihui Lin
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Driver Mutations ◽  
Small Cell Lung ◽  
Braf Mutations ◽  
Kras Mutations ◽  
Anaplastic Lymphoma

AbstractThe oncogenic driver mutations have been found that not only have potential sensitivity to epidermal growth factor receptor but also can inhibit anaplastic lymphoma kinase tyrosine kinase; more and more interest has been evoked in discovering additional targets to non-small cell lung cancer (NSCLC). Recently, many novel underlying oncogenic gene alterations have been identified, such as HER2 insertions, BRAF mutations, PIK3 mutations, FGFR1 amplifications, DDR2 mutations, KRAS mutations, MET amplification, ROS1 rearrangements, ALK rearrangements, and RET rearrangements. In this review, we will discuss the discovery of these potential targets and the application of each in NSCLC and of small molecular inhibitors on these potential targets.

scholarly journals ALK Mutation Status in EGFR-negative Non-small-cell Lung Cancer Patients in Bulgaria

Folia Medica ◽  
2018 ◽  
Vol 60 (3) ◽  
pp. 397-401
Author(s):  
Slaveyko N. Djambazov ◽  
Toni Y. Vekov ◽  
Evgeni V. Mekov ◽  
Georgi S. Slavchev ◽  
Rosen E. Petkov ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Driver Mutations ◽  
Small Cell Lung ◽  
Alk Rearrangement ◽  
Lung Cancer Patients ◽  
Anaplastic Lymphoma ◽  
Nsclc Patients

Abstract Background: Patients with non-small-cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) rearrangement mutation are found to be 3–13%. Aim: To evaluate the prevalence of ALK mutations in EGFR-negative NSCLC patients in Bulgaria. Materials and methods: One hundred and thirty-two patients with EGFR-negative NSCLC were examined for ALK mutation analysis between January and June 2016. Data were obtained from patients’ register of four major oncological hospitals in Bulgaria. Results: Data were available for 124 (93.9%) patients, tumor mass was insufficient for analysis in 8 (6.1%) patients. Most of the patients were with adenocarcinoma (82 patients, 62.1%); 11 patients (8.3%) were with squamous histology and 2 patients (1.5%) were with other type of NSCLC. Histology data were missing in 37 patients (28.0%). ALK mutation was confirmed in 5 patients (3.8%), 119 (90.2%) patients had ALK wild type. ALK positive patients were with adenocarcinoma (n=3), squamous cell carcinoma (n=1) and other type (n=1) NSCLC. All ALK mutations were observed in never smokers (n=3) and former smokers (n=2). Conclusion: The present study is the first of this kind in Bulgaria – it investigates the prevalence of ALK mutation rate in EGFR-negative NSCLC patients, which was found to be 3.8%. The presence of EGFR, ALK or other driver mutations is a prerequisite for targeted therapy and thus needs to be accurately assessed in NSCLC.

scholarly journals New Targetable Oncogenes in Non–Small-Cell Lung Cancer

2013 ◽  
Vol 31 (8) ◽  
pp. 1097-1104 ◽  
Author(s):  
Geoffrey R. Oxnard ◽  
Adam Binder ◽  
Pasi A. Jänne
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Small Cell ◽  
Driver Mutations ◽  
Small Cell Lung ◽  
Braf Mutations ◽  
Pik3ca Mutations ◽  
Anaplastic Lymphoma

The identification of oncogenic driver mutations underlying sensitivity to epidermal growth factor receptor and anaplastic lymphoma kinase tyrosine kinase inhibitors has led to a surge of interest in identifying additional targetable oncogenes in non–small-cell lung cancer. A number of new potentially oncogenic gene alterations have been characterized in recent years, including BRAF mutations, HER2 insertions, PIK3CA mutations, FGFR1 amplifications, DDR2 mutations, ROS1 rearrangements, and RET rearrangements. In this review, we will discuss the techniques used to discover each of these candidate oncogenes, the prevalence of each in non–small-cell lung cancer, the preclinical data supporting their role in lung cancer, and data on small molecular inhibitors in development.

scholarly journals Nanoparticle-Mediated Gene Silencing for Sensitization of Lung Cancer to Cisplatin Therapy

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1994 ◽  
Author(s):  
Daniel P. Feldmann ◽  
Joshua Heyza ◽  
Christoph M. Zimmermann ◽  
Steve M. Patrick ◽  
Olivia M. Merkel
Keyword(s):  
Lung Cancer ◽  
Gene Silencing ◽  
Small Cell Lung Cancer ◽  
Small Molecule ◽  
Cell Lung Cancer ◽  
Small Molecule Inhibitors ◽  
Excision Repair ◽  
Small Cell ◽  
Small Cell Lung ◽  
Platinum Based Chemotherapy

Platinum-based chemotherapy remains a mainstay treatment for the management of advanced non-small cell lung cancer. A key cellular factor that contributes to sensitivity to platinums is the 5′-3′ structure-specific endonuclease excision repair cross-complementation group 1 (ERCC1)/ xeroderma pigmentosum group F (XPF). ERCC1/XPF is critical for the repair of platinum-induced DNA damage and has been the subject of intense research efforts to identify small molecule inhibitors of its nuclease activity for the purpose of enhancing patient response to platinum-based chemotherapy. As an alternative to small molecule inhibitors, small interfering RNA (siRNA) has often been described to be more efficient in interrupting protein–protein interactions. The goal of this study was therefore to determine whether biocompatible nanoparticles consisting of an amphiphilic triblock copolymer (polyethylenimine-polycaprolactone-polyethylene glycol (PEI-PCL-PEG)) and carrying siRNA targeted to ERCC1 and XPF made by microfluidic assembly are capable of efficient gene silencing and able to sensitize lung cancer cells to cisplatin. First, we show that our PEI-PCL-PEG micelleplexes carrying ERCC1 and XPF siRNA efficiently knocked down ERCC1/XPF protein expression to the same extent as the standard siRNA transfection reagent, Lipofectamine. Second, we show that our siRNA-carrying nanoparticles enhanced platinum sensitivity in a p53 wildtype model of non-small cell lung cancer in vitro. Our results suggest that nanoparticle-mediated targeting of ERCC1/XPF is feasible and could represent a novel therapeutic strategy for targeting ERCC1/XPF in vivo.

Targeted Therapy for Non-Small Cell Lung Cancer

2020 ◽  
Vol 41 (03) ◽  
pp. 409-434 ◽  
Author(s):  
Zorawar S. Noor ◽  
Amy L. Cummings ◽  
McKenna M. Johnson ◽  
Marshall L. Spiegel ◽  
Jonathan W. Goldman
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Targeted Therapies ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Driver Mutations ◽  
Small Cell Lung ◽  
Molecular Alterations ◽  
Anaplastic Lymphoma

AbstractLung cancer is a heterogeneous disease, and the availability of comprehensive genomic profiling has allowed for the characterization of its molecular subtypes. This has increased the ability to deliver “personalized medicines” by tailoring therapies to target driver mutations in a patient's cancer. The development of targeted therapies for non-small cell lung cancer (NSCLC) has helped define the era of precision medicine throughout oncology. This article aims to contextualize recent research and provide an updated summary of targeted therapies available for patients with NSCLC. With practitioners and clinical researchers in mind, we note standard of care therapies, important approvals, practice guidelines, and treatments in development. The first section discusses mutations in the epidermal growth factor receptor (EGFR) gene, and the second section examines rearrangements in the anaplastic lymphoma kinase (ALK) and ROS1 fusions. Finally, we explore the rarer molecular alterations in BRAF, RET, MET, HER2, and KRAS. Given the many available therapies, it is important to understand the molecular alterations in NSCLC, and how to target them.

scholarly journals Evaluation of EML4-ALK Fusion Proteins in Non–Small Cell Lung Cancer Using Small Molecule Inhibitors

Neoplasia ◽  
2011 ◽  
Vol 13 (1) ◽  
pp. 1-IN1 ◽  
Author(s):  
Yongjun Li ◽  
Xiaofen Ye ◽  
Jinfeng Liu ◽  
Jiping Zha ◽  
Lin Pei
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Small Molecule ◽  
Cell Lung Cancer ◽  
Fusion Proteins ◽  
Small Molecule Inhibitors ◽  
Small Cell ◽  
Small Cell Lung
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