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Overcoming Resistance to EGFR Inhibitors in EGFR Mutant NSCLC

Overcoming Resistance to EGFR Inhibitors in EGFR Mutant NSCLC
  • Author : Anthony Faber
  • Publisher :Unknown
  • Release Date :2021-03-15
  • Total pages :250
  • ISBN : 9780128228333
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Summary : Overcoming Resistance to EGFR Inhibitors in EGFR Mutant NSCLC, Volume 17 presents updated information on how EGFR mutant lung cancers evolve to evade EGFR inhibitors, clinical strategies that identify these mechanisms, and how to implement newer therapeutic strategies to combat resistance and improve patient survival. As resistance to EGFR inhibitors is often through re-activation of MEK/ERK and PI3K pathways, or through loss of cell death responses, there is much overlap with resistance to targeted therapies in other paradigms, such as BRAF inhibitors in BRAF mutant melanoma, and HER2 inhibitors in HER2 amplified breast cancer. This book is a valuable resource for cancer researchers, clinicians, graduate students and other members of the biomedical field who are interested in promising treatments for lung cancer. Presents historical context on how NSCLC and SCLC has been treated, with an emphasis on NSCLC and how the concept of EGFR inhibitors has been implemented Discusses critical resistant mechanisms seen in the clinic to 1st, 2nd and 3rd generation EGFR inhibitors Encompasses the current state of affairs in clinical trials to address resistance

Third Generation EGFR Inhibitors

Third Generation EGFR Inhibitors
  • Author : Harun M. Patel,Rahul Pawara,Sanjay J. Surana
  • Publisher :Unknown
  • Release Date :2018-11-27
  • Total pages :208
  • ISBN : 0081026625
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Summary : Third Generation EGFR Inhibitors: Overcoming EGFR Resistance and Toxicity Problems reviews current issues relating to the design of reversible and irreversible third generation EGFR inhibitors, highlighting the types of mutation responsible for resistance, and providing different chemical starting points for researchers to optimize and develop in designing the next generation of drugs. Beginning with an introduction to EGFR inhibitors and a review of inhibitors currently approved or in clinical trials, the book goes on to discuss current approaches in the development of both covalent irreversible and covalent reversible EGFR Inhibitors. In addition, mechanisms of resistance to third generation inhibitors, and discovery of fourth generation allosteric C797S inhibitors are explored before a discussion of potential future trends. This comprehensive coverage of the design and development of improved analogues to overcome the problems of resistance and toxicity associated with third generation EGFR inhibitors makes Third Generation EGFR Inhibitors a crucial resource for medicinal chemists, drug developers, and researchers investigating cancer therapeutics. Includes full synthetic schemes of all approved and in-trial third generation inhibitors Highlights the emergence of fourth generation EGFR inhibitors and the possibilities of them overcoming constraints of third generation compounds Provides a structural correlation of third and fourth generation EGFR inhibitors, reviewing both their design strategies and typical anticancer activity

Biotargets of Cancer in Current Clinical Practice

Biotargets of Cancer in Current Clinical Practice
  • Author : Mauro Bologna
  • Publisher :Unknown
  • Release Date :2012-04-05
  • Total pages :563
  • ISBN : 161779614X
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Summary : Biotargets of Cancer in Current Clinical Practice presents an updated and reasoned review of the current status of knowledge concerning the major cancer types with a special focus on the current biomarkers, genes involved and the potential future targets of innovative therapies. The volume includes for each major cancer type, a comprehensive although concise discussion of epidemiology, affirmed and innovative biomarkers for diagnosis, and descriptions of the relevant genes for prognosis and (individualized) therapy through biotarget-specific new molecular treatments, with the latest information on the validation status of each novel biomarker. Individual chapters are dedicated to the major cancer types, plus a special chapter on metastasis. The present debate on patentability of genetic information applied to diagnostics and therapeutics of cancer is also discussed.

Current Applications for Overcoming Resistance to Targeted Therapies

Current Applications for Overcoming Resistance to Targeted Therapies
  • Author : Myron R. Szewczuk,Bessi Qorri,Manpreet Sambi
  • Publisher :Unknown
  • Release Date :2019-07-15
  • Total pages :320
  • ISBN : 303021477X
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Summary : Targeted therapies were initially developed to exploit the upregulation and dependence on key oncogenic pathways critical to cancer progression. Additionally, they also presented as a method to overcome chemoresistance by supplementing conventional therapeutic regimens with targeted therapies. However, the development of resistance to these combinatorial approaches has led to the reassessment of currently available therapeutic options to overcome resistance to targeted therapy. This book aims to provide an update on the advancements in the therapeutic arms race between cancer, clinicians and scientists alike to overcome resistance to targeted therapies. Subject experts provide a comprehensive overview of the challenges and solutions to resistance to several conventional targeted therapies in addition to providing a discussion on broad topics including targeting components of the tumor microenvironment, emerging therapeutic options, and novel areas to be explored concerning nanotechnology and the epigenome.

Resistance to Tyrosine Kinase Inhibitors

Resistance to Tyrosine Kinase Inhibitors
  • Author : Daniele Focosi
  • Publisher :Unknown
  • Release Date :2016-11-07
  • Total pages :188
  • ISBN : 3319460919
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Summary : The volume will serve as a primer on tyrosine kinase signaling and its importance in cancer. The volume will first introduce the common denominators of small-molecule and antibody-derived inhibitors, as well as the general phenomenon of resistance. The volume will then detail resistance to the most commonly used classes of tyrosine kinase inhibitors, and will focus specific chapters on resistance to BCR-ABL1, FLT3, angiokinase family members, and ALK inhibitors.

AACR 2016: Abstracts 1-2696

AACR 2016: Abstracts 1-2696
  • Author : American Association for Cancer Research (AACR)
  • Publisher :Unknown
  • Release Date :2016-03-28
  • Total pages :229
  • ISBN : 09876543XX
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Summary : The AACR Annual Meeting is a must-attend event for cancer researchers and the broader cancer community. This year's theme, "Delivering Cures Through Cancer Science," reinforces the inextricable link between research and advances in patient care. The theme will be evident throughout the meeting as the latest, most exciting discoveries are presented in every area of cancer research. There will be a number of presentations that include exciting new data from cutting-edge clinical trials as well as companion presentations that spotlight the science behind the trials and implications for delivering improved care to patients. This book contains abstracts 1-2696 presented on April 17-18, 2016, at the AACR Annual Meeting.

Chemoinformatics Approaches to Structure- and Ligand-Based Drug Design

Chemoinformatics Approaches to Structure- and Ligand-Based Drug Design
  • Author : Adriano D. Andricopulo,Leonardo L. G. Ferreira
  • Publisher :Unknown
  • Release Date :2019-02-05
  • Total pages :229
  • ISBN : 2889457443
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Summary : Chemoinformatics is paramount to current drug discovery. Structure- and ligand-based drug design strategies have been used to uncover hidden patterns in large amounts of data, and to disclose the molecular aspects underlying ligand-receptor interactions. This Research Topic aims to share with a broad audience the most recent trends in the use of chemoinformatics in drug design. To that end, experts in all areas of drug discovery have made their knowledge available through a series of articles that report state-of-the-art approaches. Readers are provided with outstanding contributions focusing on a wide variety of topics which will be of great value to those interested in the many different and exciting facets of drug design.

Guide to Targeted Therapies: Treatment Resistance in Lung Cancer

Guide to Targeted Therapies: Treatment Resistance in Lung Cancer
  • Author : Federico Cappuzzo
  • Publisher :Unknown
  • Release Date :2015-10-15
  • Total pages :67
  • ISBN : 3319207415
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Summary : This text is a concise and up-to-date review, which discusses the background, development and mechanisms of resistance, testing methods and technology, current and emerging therapies and resources that clinicians can provide to their patients. Busy healthcare professionals who want a quick review of treatment resistance in lung cancer as well as a summary of current therapies will benefit from this succinct guide.

New Drugs for Malignancy, An Issue of Hematology/Oncology Clinics of North America - E-Book

New Drugs for Malignancy, An Issue of Hematology/Oncology Clinics of North America - E-Book
  • Author : Franco Muggia
  • Publisher :Unknown
  • Release Date :2012-05-08
  • Total pages :1440
  • ISBN : 1455744085
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Summary : Topics include: Targeting IGF-1R, Tyrosine Kinase Inhibitors in Lung Cancer, Targeting mTOR, Targeting Hedgehog, Mitotic Inhibitors, Topoisomerase I Inhibitors , and New Strategies and Drugs Inhibiting Folate Pathways.

Second Line Treatment of Non-Small Cell Lung Cancer: Clinical, Pathological and Molecular Aspects of Novel Promising Drugs

Second Line Treatment of Non-Small Cell Lung Cancer: Clinical, Pathological and Molecular Aspects of Novel Promising Drugs
  • Author : Umberto Malapelle,Pierlorenzo Pallante
  • Publisher :Unknown
  • Release Date :2017-08-29
  • Total pages :229
  • ISBN : 2889452638
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Summary : Lung cancer still remains a challenging disease with a higher mortality rate in comparison to other cancers. The discovery of oncogene addicted tumours and targeted therapies responsive to these targets lead to a meaningful change in the prognosis of these diseases. Unfortunately, these newer therapeutic options are reserved to a minor part of lung cancer patients harbouring specific mutations. In the so called wild type population, the first line options bring the median overall survival to go beyond 1 year, and in the population receiving the maintenance therapy over 16 months. Given these results, more than 60% of patients may receive a second line therapy with further opportunities to improve the length and quality of life. For patients not harbouring targetable DNA mutations newer options will be available for second line therapeutic schemes and two major assets seem to be promising: immune modulation and anti-angiogenetic agents. In particular, anti PD1/PDL1 antibodies, VEGFR antibodies and TKIs, these latter combined with standard chemotherapy docetaxel advance the median overall survival of 12 months. These drugs have a different mechanism of action, various adverse events and their activity is different depending on the types of population. However, the biomarkers’ activity and efficacy prediction are not fully or totally understood. In addition, also for patients with DNA targetable mutations new drugs seems to be promising for the use in the second line therapeutic protocols. In particular, drugs selectively directed against ALK translocation and mutational events and EGFR T790M secondary mutations seems to be very promising. In this Research Topic we critically discuss the older therapies and the historical development of second line, putting in to perspective the new agents available in clinical practice. We discuss their importance from a clinical point of view, but also consider and exploit the complex molecular mechanisms responsible of their efficacy or of the subsequently observed resistance phenomena. In this perspective, the undercovering and characterization of novel predictive biomarkers by NGS technology, the characterization of novel actors in the signal transduction pathway modulating the response of the cells, the optimization of new diagnostic tool as the evaluation of liquid biopsy and the implementation of more suitable pre-clinical models are crucial aspects dissected too. Nivolumab, nintedanib and ramucirumab probably will give the opportunity to improve the efficacy outcomes for the treatment of wild type tumours in second line therapeutic schemes, but many aspects should be debated in order that these agents are made available to patients, planning ahead a therapeutic strategy, beginning from the first line therapy, to the subsequent ones in a logical and affordable manner. As well, for treatment of mutated tumours, mutated EGFR irreversible inhibitors such as rociletinib and AZD9291, and ALK targeting drugs ceritinib and alectinib will also play an important role in the immediate future. Probably the right way is to give all the available opportunities to patients, but challenges and pitfalls should be carefully debated, and by launching this Research Topic we tried to give some practical insights in this changing landscape.

Molecular Oncology, An Issue of Surgical Pathology Clinics - E-Book

Molecular Oncology, An Issue of Surgical Pathology Clinics - E-Book
  • Author : Jennifer Hunt
  • Publisher :Unknown
  • Release Date :2012-11-12
  • Total pages :240
  • ISBN : 1455750530
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Summary : Clinically accessible information for pathologists on the fast moving field of molecular pathology and oncology, addressing molecular and genetic approaches to the diagnosis and classification of tumors, predictive biomarkers for treatment response and disease progression. Recurrent in this series, summaries are provided of Key Features of tumor, Key molecular prognostic markers and therapeutic markers, Tumor suppressor genes, and Oncogenes. Topics include molecular pathology of: Breast, Gastrointestinal, Head and Neck, Genitourinary, Gynecologic, Hematopathology, Lung, Neuropathology, Pancreas/Biliary, and Sarcome.

Targeted Therapies in Lung Cancer: Management Strategies for Nurses and Practitioners

Targeted Therapies in Lung Cancer: Management Strategies for Nurses and Practitioners
  • Author : Marianne Davies,Beth Eaby-Sandy
  • Publisher :Unknown
  • Release Date :2019-07-16
  • Total pages :120
  • ISBN : 3030165507
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Summary : This book aims to educate nurses and advanced practice providers (APP’s) about known mutations, availability of targeted therapy and the management of patients with non-small cell lung cancer (NSCLC). It will educate nurses and practitioners about the scope of therapy to assure safe and effective lung cancer treatment. In this era of personalized medicine, nurses and APP’s are responsible for guiding patients from diagnosis through treatment. This starts with the identification of patients that can benefit from these therapies, the key role of biopsy acquisition (ie. what to test, when and how often) and treatment selection based on the mutation identified. Readers will learn about the mechanisms of action, administration, potential adverse side effects and unique management strategies for these targeted agents. Lung cancer continues to be the leading cause of cancer death in the United States and worldwide. Recent advances in the identification of specific oncogenic mutations that drive cancer development, growth and metastasis have led to major paradigm shifts in lung cancer treatment. Sophisticated methods are required to identify specific mutations at the time of diagnosis. This book explains how molecularly targeted therapies have been developed that target these drivers. To date, several tyrosine kinase inhibitors have been approved to target the epidermal growth factor receptor (EGFR), EML4-ALK ,ROS1 and BRAF. Most recently, immune checkpoint inhibitors have been approved with some indication that efficacy may be enhanced for patients who overexpress PD-L1. While some driver mutations have been identified, there is ongoing investigation into additional mutations. In the case of driver mutations, lung cancers will develop resistance to therapy. This book provides nurses and APP’s with the mechanisms of resistance that have been identified such as T790 mutation and many others in the EGFR mutation, and shows how the next level of drug development is focused on identifying mechanisms of resistance and development of new agents that overcome these mutations. With this book in hand, nurses and practitioners will be able to navigate patients through this ever expanding field of lung cancer treatment.

Successes and Limitations of Targeted Cancer Therapy

Successes and Limitations of Targeted Cancer Therapy
  • Author : S. Peters,R.A. Stahel
  • Publisher :Unknown
  • Release Date :2014-02-19
  • Total pages :124
  • ISBN : 3318025429
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Summary : The treatment of patients with advanced malignancies has undergone remarkable change in the last few years. While in the past decisions about systemic therapy were largely based on the performance status of a patient, oncologists today also take into account the pathological and molecular characteristics of the patient’s tumor. Targeting specific molecular pathways important for tumorigenesis has become the preferred way of treatment for many types of malignancies. With these advances come new challenges including the optimization of therapy, recognizing and dealing with side effects and, importantly, the development of resistance. This book provides an up-to-date overview of the advances and limitations of targeted therapy for several tumor entities including breast cancer, colon cancer, gastrointestinal stromal tumors, lung cancer, melanoma, ovarian cancer and renal cell carcinoma. Written by over a dozen internationally renowned scientists, the book is suitable for advanced students, postdoctoral researchers, scientists and clinicians who wish to update their knowledge of the latest approaches to targeted cancer therapies.

Cancer Research

Cancer Research
  • Author : Anonim
  • Publisher :Unknown
  • Release Date :2008
  • Total pages :229
  • ISBN : 09876543XX
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Summary :

EGFR Inhibitors—Advances in Research and Application: 2013 Edition

EGFR Inhibitors—Advances in Research and Application: 2013 Edition
  • Author : Anonim
  • Publisher :Unknown
  • Release Date :2013-06-21
  • Total pages :69
  • ISBN : 1481675176
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Summary : EGFR Inhibitors—Advances in Research and Application: 2013 Edition is a ScholarlyBrief™ that delivers timely, authoritative, comprehensive, and specialized information about Lapatinib in a concise format. The editors have built EGFR Inhibitors—Advances in Research and Application: 2013 Edition on the vast information databases of ScholarlyNews.™ You can expect the information about Lapatinib in this book to be deeper than what you can access anywhere else, as well as consistently reliable, authoritative, informed, and relevant. The content of EGFR Inhibitors—Advances in Research and Application: 2013 Edition has been produced by the world’s leading scientists, engineers, analysts, research institutions, and companies. All of the content is from peer-reviewed sources, and all of it is written, assembled, and edited by the editors at ScholarlyEditions™ and available exclusively from us. You now have a source you can cite with authority, confidence, and credibility. More information is available at http://www.ScholarlyEditions.com/.

Targeted Therapies for Lung Cancer

Targeted Therapies for Lung Cancer
  • Author : Ravi Salgia
  • Publisher :Unknown
  • Release Date :2019-06-26
  • Total pages :238
  • ISBN : 3030178323
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Summary : This book contextualizes translational research and provides an up to date progress report on therapies that are currently being targeted in lung cancer. It is now well established that there is tremendous heterogeneity among cancer cells both at the inter- and intra-tumoral level. Further, a growing body of work highlights the importance of targeted therapies and personalized medicine in treating cancer patients. In contrast to conventional therapies that are typically administered to the average patient regardless of the patient’s genotype, targeted therapies are tailored to patients with specific traits. Nonetheless, such genetic changes can be disease-specific and/or target specific; thus, the book addresses these issues manifested in the somatically acquired genetic changes of the targeted gene. Each chapter is written by a leading medical oncologist who specializes in thoracic oncology and is devoted to a particular target in a specific indication. Contributors provide an in-depth review of the literature covering the mechanisms underlying signaling, potential cross talk between the target and downstream signaling, and potential emergence of drug resistance.

Immunohistochemistry II

Immunohistochemistry II
  • Author : A. C. Cuello
  • Publisher :Unknown
  • Release Date :1993-07-20
  • Total pages :456
  • ISBN : 09876543XX
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Summary : Leading international experts describe both novel and established immunohistochemical techniques and interpret results and validity regarding the various methods used, particularly in the investigation of the nervous system. Coverage includes the immunocytochemistry (ICC) of second messenger molecules, applications of confocal microscopy to ICC, the latest pre-embedding and dual labeling EM techniques, anterograde PHAL tracing and more.

Lung Cancer and Personalized Medicine

Lung Cancer and Personalized Medicine
  • Author : Aamir Ahmad,Shirish Gadgeel
  • Publisher :Unknown
  • Release Date :2015-12-14
  • Total pages :228
  • ISBN : 3319242237
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Summary : This, the first of two volumes on personalized medicine in lung cancer, touches on the core issues related to the understanding of lung cancer—statistics and epidemiology of lung cancer—along with the incidence of lung cancer in non-smokers. A major focus of this volume is the state of current therapies against lung cancer—immune, targeted therapies against EGFR TKIs, KRAS, ALK, angiogenesis; the associated challenges, especially resistance mechanisms; and recent progress in targeted drug development based on metal chemistry. Chapters are written by some of the leading experts in the field, who provide a better understanding of lung cancer, the factors that make it lethal, and current research focused on developing personalized treatment plans. With a unique mix of topics, this volume summarizes the current state-of-knowledge on lung cancer and the available therapies.

Cancer Evolution

Cancer Evolution
  • Author : Charles Swanton
  • Publisher :Unknown
  • Release Date :2017
  • Total pages :350
  • ISBN : 9781621821434
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Summary : Tumor progression is driven by mutations that confer growth advantages to different subpopulations of cancer cells. As a tumor grows, these subpopulations expand, accumulate new mutations, and are subjected to selective pressures from the environment, including anticancer interventions. This process, termed clonal evolution, can lead to the emergence of therapy-resistant tumors and poses a major challenge for cancer eradication efforts. Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Medicine examines cancer progression as an evolutionary process and explores how this way of looking at cancer may lead to more effective strategies for managing and treating it. The contributors review efforts to characterize the subclonal architecture and dynamics of tumors, understand the roles of chromosomal instability, driver mutations, and mutation order, and determine how cancer cells respond to selective pressures imposed by anticancer agents, immune cells, and other components of the tumor microenvironment. They compare cancer evolution to organismal evolution and describe how ecological theories and mathematical models are being used to understand the complex dynamics between a tumor and its microenvironment during cancer progression. The authors also discuss improved methods to monitor tumor evolution (e.g., liquid biopsies) and the development of more effective strategies for managing and treating cancers (e.g., immunotherapies). This volume will therefore serve as a vital reference for all cancer biologists as well as anyone seeking to improve clinical outcomes for patients with cancer.

Pocket Oncology

Pocket Oncology
  • Author : Alexander Drilon,Michael Postow,Neil Vasan,Maria I. Carlo
  • Publisher :Unknown
  • Release Date :2018-02-07
  • Total pages :374
  • ISBN : 1496391055
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Summary : Written and edited by leading cancer experts at Memorial Sloan Kettering Cancer Center, Pocket Oncology, Second Edition, is a practical, high-yield reference for trainees and practitioners of medical oncology and hematology. This easy-to-use, loose-leaf resource contains up-to-date information essential to caring for patients with cancer, from cancer biology, prevention, screening, treatment and supportive care to new advances in immuno-oncology and precision medicine.

Central Nervous System Metastases in Lung Cancer Patients: From Prevention to Diagnosis and Treatment

Central Nervous System Metastases in Lung Cancer Patients: From Prevention to Diagnosis and Treatment
  • Author : Lizza E.L Hendriks,Deepa S. Subramaniam,Anne-Marie C. Dingemans
  • Publisher :Unknown
  • Release Date :2019-01-21
  • Total pages :94
  • ISBN : 2889457079
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Summary : Approximately 40% of lung cancer patients will develop central nervous system (CNS) metastases during the course of their disease. Most of these are brain metastases, but up to 10% will develop leptomeningeal metastases. Known risk factors for CNS metastases development are small cell lung cancer (SCLC), adenocarcinoma histology, epidermal growth factor receptor (EGFR) mutant or anaplastic lymphoma kinase (ALK) rearranged lung cancer, advanced nodal status, tumor stage and younger age. CNS metastases can have a negative impact on quality of life (QoL) and overall survival (OS). The proportion of lung cancer patients diagnosed with CNS metastases has increased over the years due to increased use of brain imaging as part of initial cancer staging, advances in imaging techniques and better systemic disease control. Post contrast gadolinium enhanced magnetic resonance imaging (gd-MRI) is preferred, however when this is contra-indicated a contrast enhanced computed tomography (CE-CT) is mentioned as an alternative option. When CNS metastases are diagnosed, local treatment options consist of radiotherapy (stereotactic or whole brain) and surgery. Local treatment can be complicated by symptomatic radiation necrosis for which no high level evidence based treatment exists. Moreover, differential diagnosis with metastasis progression is difficult. Systemic treatment options have expanded over the last years. Until recently, chemotherapy was the only treatment option with a poor penetration in the CNS. Angiogenesis inhibitors are promising in the treatment of primary CNS tumors as well as radiation necrosis but clinical trials of anti-angiogenic agents in NSCLC have largely excluded patients with CNS metastases. Furthermore, research has also focused on methods to prevent development of CNS disease, for example with prophylactic cranial irradiation. Recently, checkpoint inhibitors have become available for NSCLC patients, and tyrosine kinase inhibitors (TKIs) have improved prognosis significantly in those with a druggable driver mutation. Newer TKIs are often designed to have better CNS penetration compared to first-generation TKIs. Despite advances in treatment options CNS metastases remain a problem in lung cancer and cause morbidity and mortality. This Research Topic provides an extensive resource of articles describing advances in CNS metastases management in lung cancer patients, from prevention to diagnosis and treatment.