Third Generation Egfr Inhibitors

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

Overcoming Resistance to EGFR Inhibitors in EGFR Mutant NSCLC 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

Epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) is a clinically important driver alteration affecting approximately one-third of lung cancer patients. Treatments for EGFR-exon 19 deletion and exon 21 L858R NSCLC have evolved over the last decade from first-generation reversible tyrosine kinase inhibitors (TKI) to third-generation irreversible TKIs, of which osimertinib has been the widely accepted as first-line therapy. Despite survival improvement seen with osimertinib and its efficacy against acquired T790M mutation, resistance through on-target and off-target pathways eventually develop. This Element describes the structural biology and pathophysiology of EGFR-mutant NSCLC and discusses past, current, and future treatment options in the metastatic, neoadjuvant, and adjuvant settings. It describes the biology and recently approved treatment for EGFR-exon 20 insertion mutation and the treatment for the uncommon exon 18 (G719X), 20 (S768I), and 21 (L861Q) mutations. It also outlines the promising clinical applications of circulating tumor DNA (ctDNA).

This book explains the pharmacological relationships between the various systems in the human body. It offers a comprehensive overview of the pharmacology concerning the autonomic, central, and peripheral nervous systems. Presenting up-to-date information on chemical mediators and their significance, it highlights the therapeutic aspects of several diseases affecting the cardiovascular, renal, respiratory, gastrointestinal, endocrinal, and hematopoietic systems. The book also includes drug therapy for microbial and neoplastic diseases. It also comprises sections on immunopharmacology, dermatological, and ocular pharmacology providing valuable insights into these emerging and recent topics. Covering the diverse groups of drugs acting on different systems, the book reviews their actions, clinical uses, adverse effects, interactions, and subcellular mechanisms of action. It is divided into 11 parts, subdivided into several chapters that evaluate the basic pharmacological principles that govern the different types of body systems. This book is intended for academicians, researchers, and clinicians in industry and academic institutions in pharmaceutical, pharmacological sciences, pharmacy, medical sciences, physiology, neurosciences, biochemistry, molecular biology and other allied health sciences.

Protein tyrosine kinase (PTK) deregulation contributes to growth of cancer and many other diseases. The development of small-molecule tyrosine kinase inhibitors (TKIs) that target the deregulated PTKs, such as epidermal growth factor receptor (EGFR) in non-small-cell lung cancer (NSCLC) and Bcr-ABL in chronic myeloid leukemia (CML), has revolutionized disease management. In this book, we examine a few aspects of PTKs and cancer, considering efficacy, predictive markers to therapeutic response, limitations, and future directions in TKI treatment. In this rapidly evolving field, overcoming therapeutic resistance is most challenging, and multi-targeting directs the next-generation TKIs and combination therapy as ongoing strategies in cancer treatment.

Tyrosine Kinase Inhibitors as Sensitizing Agents for Chemotherapy, the fourth volume in the Cancer Sensitizing Agents for Chemotherapy Series, focuses on strategic combination therapies that involve a variety of tyrosine kinase inhibitors working together to overcome multi-drug resistance in cancer cells. The book discusses several tyrosine kinase inhibitors that have been used as sensitizing agents, such as EGFR, BCR-ABL, ALK and BRAF. In each chapter, readers will find comprehensive knowledge on the inhibitor and its action, including its biochemical, genetic, and molecular mechanisms' emphases. This book is a valuable source for oncologists, cancer researchers and those interested in applying new sensitizing agents to their research in clinical practice and in trials. Summarizes the sensitizing role of some tyrosine kinase inhibitors in existing research Brings recent findings in several cancer types, both experimental and clinically, with a particular emphases on underlying biochemical, genetic, and molecular mechanisms Provides an updated and comprehensive knowledge regarding the field of combinational cancer treatment

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.