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 PHARMACOTHERAPY OF NON-SMALL CELL LUNG CANCER: A SHORT REVIEW

2018 ◽  
Vol 11 (3) ◽  
pp. 7
Author(s):  
Balaji O
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Targeted Therapies ◽  
Advanced Disease ◽  
Growth Factor Receptor ◽  
The United States ◽  
Small Cell ◽  
Small Cell Lung ◽  
Anaplastic Lymphoma

 Lung cancer is a global health problem with non-small cell lung cancer (NSCLC) being the most common histopathological variant causing almost 28% deaths in the United States of America. Platinum compounds were the mainstay of treatment, and since past 10 years, various newer targeted therapies have come into play. Epidermal growth factor receptor and anaplastic lymphoma kinase mutations play a major role in the development of advanced disease. Hence, targeted therapies and immunotherapies will remain an integral part in the management of advanced disease. Hence, this review focuses on the newer drugs approved by Food and Drug Administration to treat NSCLC

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 Targeted Molecular Treatments in Non-Small Cell Lung Cancer: A Clinical Guide for Oncologists

2018 ◽  
Vol 7 (8) ◽  
pp. 192 ◽  
Author(s):  
Kim Tam Bui ◽  
Wendy A. Cooper ◽  
Steven Kao ◽  
Michael Boyer
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Growth Factor Receptor ◽  
Resistance Mechanisms ◽  
Small Cell ◽  
Current Evidence ◽  
Cancer Therapies ◽  
Small Cell Lung ◽  
Anaplastic Lymphoma

Targeted molecular treatments have changed the way non-small cell lung cancer (NSCLC) is managed. Epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), v-raf murine sarcoma viral oncogene homolog B1 (BRAF), and c-ros oncogene 1 (ROS1) mutations are now used to guide specific anti-cancer therapies to improve patient outcomes. New targeted molecular treatments are constantly being developed and evaluated as a means to improve efficacy, overcome resistance, or minimise toxicity. This review article summarises the current evidence for the efficacy, resistance mechanisms, and safety of targeted molecular treatments against specific mutations in NSCLC.

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 Immunotherapy and Targeted Therapies in the Treatment of Non-small Cell Lung Cancer

2017 ◽  
Vol 13 (01) ◽  
pp. 35
Author(s):  
Tu Nguyen-Ngoc ◽  
Martin Reck ◽  
Daniel SW Tan ◽  
Solange Peters ◽  
◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Targeted Therapies ◽  
Checkpoint Inhibitors ◽  
Genetic Alterations ◽  
Small Cell ◽  
Egfr Mutations ◽  
Small Cell Lung ◽  
Anaplastic Lymphoma

In the last decade, the emergence of targeted therapies has changed the treatment paradigm for non-small cell lung cancer (NSCLC). The growing availability of therapies targeting specific genetic alterations, such as epidermal growth factor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements, have led to changes in the guidelines to reflect the need for molecular profiling. More recently, immunotherapeutic approaches have been investigated in the treatment setting of NSCLC, and these may provide superior outcomes and have substantially better tolerability compared to chemotherapy. Immunotherapies currently available for NSCLC include the checkpoint inhibitors anti-PD-1 antibodies nivolumab and pembrolizumab. Several other anti-PD-L1 compounds such as atezolizumab, durvalumab and avelumab are also very advanced in clinical investigation, in monotherapy as well as in combination with immune priming phase activators anti-CTLA4 ipilimumab and tremelimumab, across all treatment lines. The challenge facing oncologists is identifying which therapy is best suited to the individual patient.

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.

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.

scholarly journals FGFR1 is critical for Rbl2 loss-driven tumor development and requires PLCG1 activation for continued growth of small cell lung cancer

2019 ◽  
Author(s):  
Kee-Beom Kim ◽  
Youngchul Kim ◽  
Dong-Wook Kim ◽  
Kwon-Sik Park
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Targeted Therapies ◽  
Tumor Development ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Tyrosine Kinase Receptor ◽  
Small Cell Lung ◽  
Physiological Impact

AbstractSmall cell lung cancer (SCLC) remains a recalcitrant disease; limited therapeutic options have not improved overall survival and approved targeted therapies are lacking. Amplification of the tyrosine kinase receptor FGFR1 (fibroblast growth factor receptor 1) is one of the few actionable alterations found in SCLC genome. However, efforts to develop targeted therapies for FGFR1-amplified SCLC are hindered by critical gaps in knowledge around the molecular origins and mediator of FGFR1-driven signalling and the physiological impact of targeting FGFR1. Here we demonstrate the oncogenic impact of increased FGFR1 on the malignant progression of precancerous cells and the necessity of nonamplified FGFR1 for SCLC development and homeostasis. Unexpected dependency of Rbl2 loss-driven tumor development on FGFR1 in autochthonous mouse models reveals a novel function of p130 (encoded by Rbl2), a member of the RB family of tumor suppressors, as a regulator of FGFR1 expression. Additionally, FGFR1-dependent SCLC cells require activation of PLCG1 for continued growth. Together, this study uncovers mechanisms of FGFR1-driven SCLC that involves p130 upstream and PLCG1 downstream and provides potential biomarkers for anti-FGFR1 therapeutic strategy.

scholarly journals Molecular Epidemiology of the Main Druggable Genetic Alterations in Non-Small Cell Lung Cancer

2021 ◽  
Vol 22 (2) ◽  
pp. 612
Author(s):  
Sara S. Fois ◽  
Panagiotis Paliogiannis ◽  
Angelo Zinellu ◽  
Alessandro G. Fois ◽  
Antonio Cossu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Molecular Epidemiology ◽  
Cell Lung Cancer ◽  
Targeted Therapies ◽  
Prognostic Significance ◽  
Genetic Alterations ◽  
Small Cell ◽  
Driver Mutations ◽  
Small Cell Lung

Lung cancer is the leading cause of death for malignancy worldwide. Its molecular profiling has enriched our understanding of cancer initiation and progression and has become fundamental to provide guidance on treatment with targeted therapies. Testing the presence of driver mutations in specific genes in lung tumors has thus radically changed the clinical management and outcomes of the disease. Numerous studies performed with traditional sequencing methods have investigated the occurrence of such mutations in lung cancer, and new insights regarding their frequency and clinical significance are continuously provided with the use of last generation sequencing technologies. In this review, we discuss the molecular epidemiology of the main druggable genetic alterations in non-small cell lung cancer, namely EGFR, KRAS, BRAF, MET, and HER2 mutations or amplification, as well as ALK and ROS1 fusions. Furthermore, we investigated the predictive impact of these alterations on the outcomes of modern targeted therapies, their global prognostic significance, and their mutual interaction in cases of co-occurrence.

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