third generation egfr inhibitors

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Third Generation EGFR Inhibitors
Author : Harun M. Patel,Rahul Pawara,Sanjay J. Surana
Publisher : Elsevier
Release Date : 2018-11-27
ISBN 10 : 0081026625
Pages : 208 pages
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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

Second Line Treatment of Non-Small Cell Lung Cancer: Clinical, Pathological and Molecular Aspects of Novel Promising Drugs
Author : Umberto Malapelle,Pierlorenzo Pallante
Publisher : Frontiers Media SA
Release Date : 2017-08-29
ISBN 10 : 2889452638
Pages : 329 pages
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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.

Frontiers in Anti-Cancer Drug Discovery: Volume 11
Author : Atta-ur-Rahman ,Muhammad Iqbal Choudhary
Publisher : Bentham Science Publishers
Release Date : 2020-09-01
ISBN 10 : 9811422125
Pages : 163 pages
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Frontiers in Anti-Cancer Drug Discovery is a book series devoted to publishing the latest advances in anti-cancer drug design and discovery. In each volume, eminent scientists contribute reviews relevant to all areas of rational drug design and drug discovery including medicinal chemistry, in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, recent important patents, and structure-activity relationships. The book series should prove to be of interest to all pharmaceutical scientists involved in research in anti-cancer drug design and discovery. The book series is essential reading to all scientists involved in drug design and discovery who wish to keep abreast of rapid and important developments in the field. The eleventh volume of the series focuses on reviews on targeted therapies and drug delivery systems. This volume covers the following topics: - PI3K/Akt/mTOR Pathway in Acute Lymphoblastic Leukemia Targeted Therapies - Polymeric Nanomedicines in Treatment of Breast Cancer: Review of Contemporary Research - Treatment of Lung Cancer in the New Era - Oral Administration of Cancer Chemotherapeutics Exploiting Self-Nanoemulsifying Drug Delivery System: Recent Progress and Application - Targeting Approaches for the Diagnosis and Treatment of Cancer.

A Beginner's Guide to Targeted Cancer Treatments
Author : Elaine Vickers
Publisher : John Wiley & Sons
Release Date : 2018-05-08
ISBN 10 : 1119126835
Pages : 360 pages
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The accessible guide to the principles behind new, more targeted drug treatments for cancer Written for anyone who encounters cancer patients, cancer data or cancer terminology, but have no more than a passing knowledge of cell biology. A Beginner's Guide to Targeted Cancer Treatments provides an understanding of how cancer works and the many new treatments available. Using over 100 original illustrations, this accessible handbook covers the biology and mechanisms behind a huge range of targeted drug treatments, including many new immunotherapies. Dr Vickers translates a complex and often overwhelming topic into something digestible and easily understood. She also explains what cancer is, how it behaves and how our understanding of cancer has changed in recent years. Each chapter takes the reader through how new cancer drugs work and their benefits and limitations. With the help of this book, readers will be able to better understand more complex, in-depth articles in journals and books and develop their knowledge. This vital resource: Offers the latest insights into cancer biology Provides a broad understanding of how targeted cancer treatments work Describes many of the new immunotherapy approaches to cancer treatment, such as checkpoint inhibitors and CAR-modified T cells Helps readers feel confident discussing treatment options with colleagues and patients Provides an overview of which treatments are relevant to each of the most common solid tumours and haematological cancers, and the rationale behind them Demystifies the jargon – terms such as the EMT, cancer stem cells, monoclonal antibodies, kinase inhibitors, angiogenesis inhibitors etc. Explains the resistance mechanisms to many new treatments, including issues such as the way cancer cells diversify and evolve and the complex environment in which they live

Molecular Mechanisms of Acquired Resistance to Third-generation EGFR-TKIs in EGFR T790M-mutant Lung Cancer
Author : N.A
Publisher : N.A
Release Date : 2018
ISBN 10 :
Pages : 329 pages
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Abstract Lung cancer represents the leading cause of cancer-related deaths worldwide. Despite great advances in its management with the recent emergence of molecular targeted therapies for non-small-cell lung cancer (NSCLC), relapse of the metastatic disease always occurs within approximately one year. Epidermal growth factor receptor (EGFR) mutant tumours are the prime example of oncogene addiction and clonal evolution in oncology, regarding the emergence of resistance to first- and second-generation EGFR inhibitors. Multiple studies have revealed that the EGFR-T790M gatekeeper mutation is the main cause of tumour escape. Recently, irreversible pyrimidine-based EGFR inhibitors especially designed for this particular setting have shown robust clinical activity. However, similar to first- and second-generation inhibitors, the development of a diversified set of resistance mechanisms in response to these new compounds is an emerging issue. To date, clinical management of this growing number of patients has not been clearly established, even if anecdotal responses to subsequent molecularly guided therapies have been observed. By exhaustively reviewing and classifying all the preclinical and clinical data published on resistance to third-generation EGFR inhibitors in NSCLC, this work reveals the heterogeneity of the mechanisms that a tumour can develop to evade therapeutic pressure. Strategies currently being tested in clinical trials are discussed in light of these findings.

Chemoinformatics Approaches to Structure- and Ligand-Based Drug Design
Author : Adriano D. Andricopulo,Leonardo L. G. Ferreira
Publisher : Frontiers Media SA
Release Date : 2019-02-05
ISBN 10 : 2889457443
Pages : 329 pages
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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.

Osimertinib and Other Third-generation EGFR TKI in EGFR-mutant NSCLC Patients
Author : N.A
Publisher : N.A
Release Date : 2018
ISBN 10 :
Pages : 329 pages
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Abstract Osimertinib was the first third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) to receive FDA and EMA approval for metastatic EGFR-mutant non-small-cell lung cancer (NSCLC) patients that have acquired the EGFR T790M resistance mutation. Clinical trials have demonstrated the efficacy of osimertinib in this patient population and clinical trials of other third-generation EGFR TKI are currently under way. Additional challenges in this patient population, such as the upfront efficacy of osimertinib, validation of T790M in liquid biopsies as a dynamic predictive marker of efficacy, along with combination with immune checkpoint inhibitors are being explored, representing an extraordinary time of development for EGFR-mutant NSCLC.

Resistance to Tyrosine Kinase Inhibitors
Author : Daniele Focosi
Publisher : Springer
Release Date : 2016-12-11
ISBN 10 : 9783319460901
Pages : 188 pages
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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.

Summers And Winters At Balmwhapple: By The North Sea
Author : Sir John Skelton
Publisher : Wentworth Press
Release Date : 2019-03-27
ISBN 10 : 9781011581078
Pages : 272 pages
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This work has been selected by scholars as being culturally important, and is part of the knowledge base of civilization as we know it. This work was reproduced from the original artifact, and remains as true to the original work as possible. Therefore, you will see the original copyright references, library stamps (as most of these works have been housed in our most important libraries around the world), and other notations in the work. This work is in the public domain in the United States of America, and possibly other nations. Within the United States, you may freely copy and distribute this work, as no entity (individual or corporate) has a copyright on the body of the work. As a reproduction of a historical artifact, this work may contain missing or blurred pages, poor pictures, errant marks, etc. Scholars believe, and we concur, that this work is important enough to be preserved, reproduced, and made generally available to the public. We appreciate your support of the preservation process, and thank you for being an important part of keeping this knowledge alive and relevant.

Adverse Events and Oncotargeted Kinase Inhibitors
Author : Giuseppe Tridente
Publisher : Academic Press
Release Date : 2017-05-08
ISBN 10 : 0128094451
Pages : 736 pages
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Adverse Events and Oncotargeted Kinase Inhibitors gathers and evaluates data on adverse events associated with tyrosine kinase inhibitors (TKIs), a powerful anti-tumor drug class that has recently been introduced for human therapy. This book compiles a comprehensive safety profile of each TKI from experiences in official therapeutic indications, also exploring off-label exploratory investigations and postmarketing pharmaceutical surveillance databases. A brief history of each drug’s development and submission is provided, along with a more detailed analysis of the mechanism(s) of action involved in therapeutic activity or related to the insurgence of specific adverse events. Early chapters focus on general characteristics of TKIs, typology, and classification of adverse events, while the final chapters analyze TKIs as AE inducers and classes of AEs by system or organ involvement. This comprehensive resource compiles and critically reviews all of the relevant safety data for this class of drugs, with the goal of improving the understanding of pathogenesis and facilitating the prevention, monitoring, and management of these adverse events. Offers a unique and comprehensive publication on the adverse events associated with a new and fast-growing class of medicines Provides a systematic analysis of adverse events aimed at better prevention through understanding and offering insights for the development of safer drugs Uses practical guidelines to establish a leading reference on this class of drugs for educators, researchers, drug developers, clinicians, safety professionals, and more

Central Nervous System Metastases
Author : Manmeet Ahluwalia,Philippe Metellus,Riccardo Soffietti
Publisher : Springer Nature
Release Date : 2019-11-05
ISBN 10 : 3030234177
Pages : 421 pages
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This book provides a comprehensive overview of brain metastases, from the molecular biology aspects to therapeutic management and perspectives. Due to the increasing incidence of these tumors and the urgent need to effectively control brain metastatic diseases in these patients, new therapeutic strategies have emerged in recent years. The volume discusses all these innovative approaches combined with new surgical techniques (fluorescence, functional mapping, integrated navigation), novel radiation therapy techniques (stereotactic radiosurgery) and new systemic treatment approaches such as targeted- and immunotherapy. These combination strategies represent a new therapeutic model in brain metastatic patients in which each medical practitioner (neurosurgeon, neurologist, medical oncologist, radiation oncologist) plays a pivotal role in defining the optimal treatment in a multidisciplinary approach. Written by recognized experts in the field, this book is a valuable tool for neurosurgeons, neuro-oncologists, neuroradiologists, medical oncologists, radiation oncologists, cognitive therapists, basic scientists and students working in the area of brain tumors.

Target Validation in Drug Discovery
Author : Brian W. Metcalf,Susan Dillon
Publisher : Elsevier
Release Date : 2011-04-28
ISBN 10 : 9780080465975
Pages : 296 pages
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This work presents a comprehensive contemporary framework for approaching target validation in drug discovery. It begins with a detailed description of new enabling technologies, including aptamers, RNA interference, functional genomics, and proteomics. The next section looks at biologic drug development with in-depth discussion of lessons learned from such well-known cases as Erbitux, Herceptin, and Avastin. Additional targets known as "second generation" drugs, which can be identified when disease pathways are validated by biologics, present new possible small molecule therapeutics and serve as the focus of the final section of the book.

Colorectal Cancer
Author : Jindong Chen
Publisher : BoD – Books on Demand
Release Date : 2018-05-16
ISBN 10 : 1789231000
Pages : 128 pages
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With international experts sharing their experience and knowledge on these different aspects in the management of colorectal cancer, this book has this opportunity to offer all physicians treating colorectal cancer, as well as researchers, updated information concerning the biology, diagnosis, screening, and treatment of colorectal carcinoma. This book provides a detailed evaluation of diagnostic modalities, in-depth analysis of screening for colorectal cancer, recent advances in treatment, and principles and trends in the management of colorectal cancer. This updated knowledge will be an interesting and informative read for any clinician involved in the management of patients with colorectal cancer. In addition, readers such as related physicians, researchers, and colorectal cancer patients are potential beneficiaries of this book.

Lung Cancer and Personalized Medicine
Author : Aamir Ahmad,Shirish Gadgeel
Publisher : Springer
Release Date : 2015-12-14
ISBN 10 : 3319242237
Pages : 228 pages
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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.

Medicinal Chemistry for Practitioners
Author : Jie Jack Li
Publisher : John Wiley & Sons
Release Date : 2020-06-29
ISBN 10 : 1119607302
Pages : 416 pages
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Presenting both a panoramic introduction to the essential disciplines of drug discovery for novice medicinal chemists as well as a useful reference for veteran drug hunters, this book summarizes the state-of-the-art of medicinal chemistry. It covers key drug targets including enzymes, receptors, and ion channels, and hit and lead discovery. The book hen surveys a drug's pharmacokinetics and toxicity, with a solid chapter covering fundamental bioisosteres as a guide to structure-activity relationship investigations.

Molecular Pathology of Lung Cancer
Author : Philip T. Cagle,Timothy Craig Allen,Mary Beth Beasley,Lucian R. Chirieac,Sanja Dacic,Alain C. Borczuk,Keith M. Kerr
Publisher : Springer Science & Business Media
Release Date : 2012-06-14
ISBN 10 : 1461431972
Pages : 216 pages
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As with other books in the Molecular Pathology Library Series, Molecular Pathology of Lung Cancer bridges the gap between the molecular specialist and the clinical practitioner, including the surgical pathologist who now has a key role in decisions regarding molecular targeted therapy for lung cancer. Molecular Pathology of Lung Cancer provides the latest information and current insights into the molecular basis for lung cancer, including precursor and preinvasive lesions, molecular diagnosis, molecular targeted therapy, molecular prognosis, molecular radiology and related fields for lung cancer generally and for the specific cell types. As many fundamental concepts about lung cancer have undergone revision in only the past few years, this book will likely be the first to comprehensively cover the new molecular pathology of lung cancer. It provides a foundation in this field for pathologists, medical oncologists, radiation oncologists, thoracic surgeons, thoracic radiologists and their trainees, physician assistants, and nursing staff.

Molecular Targeted Therapy of Lung Cancer
Author : Yuichi Takiguchi
Publisher : Springer
Release Date : 2017-01-24
ISBN 10 : 9811020027
Pages : 327 pages
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This book discusses the latest molecular targeted therapy of lung cancer including its evaluation and future directions. It clearly illustrates the initial dramatic effectiveness of molecular targeted therapy, recurrence of the disease, overcoming the wide variety of resistance mechanisms using new-generation molecular targeted agents and potential novel approaches. It also outlines the increasing necessity for new diagnostic technology and strategies for managing different adverse effects and novel methods for evaluating effectiveness and safety. Edited and authored by opinion leaders, Molecular Targeted Therapy of Lung Cancer provides a comprehensive overview of the disease and its treatments. It is a valuable resource for graduate students, post-doctoral fellows and faculty staff, as well as researchers involved in clinical and translational research on lung cancer, helping promote new ideas for further advances.

Successes and Limitations of Targeted Cancer Therapy
Author : S. Peters,R.A. Stahel
Publisher : Karger Medical and Scientific Publishers
Release Date : 2014-02-19
ISBN 10 : 3318025429
Pages : 124 pages
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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.

Guide to Targeted Therapies: Treatment Resistance in Lung Cancer
Author : Federico Cappuzzo
Publisher : Springer
Release Date : 2015-10-15
ISBN 10 : 3319207415
Pages : 67 pages
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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.

Drug Discovery and Development
Author : Omboon Vallisuta,Suleiman Olimat
Publisher : BoD – Books on Demand
Release Date : 2015-06-03
ISBN 10 : 9535121286
Pages : 330 pages
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It is very important for scientists all over the globe to enhance drug discovery research for better human health. This book demonstrates that various expertise are essential for drug discovery including synthetic or natural drugs, clinical pharmacology, receptor identification, drug metabolism, pharmacodynamic and pharmacokinetic research. The following 5 sections cover diverse chapter topics in drug discovery: Natural Products as Sources of Leading Molecules in Drug Discovery; Oncology and Drug Discovery; Receptors Involvement in Drug Discovery; Management and Development of Drugs against Infectious Diseases; Advanced Methodology.