Download or read book Therapeutic Strategies to Overcome ALK Resistance in Cancer written by Luc Friboulet and published by Academic Press. This book was released on 2021-01-05 with total page 218 pages. Available in PDF, EPUB and Kindle. Book excerpt: Therapeutic Strategies to Overcome ALK Resistance in Cancer, Volume 13, presents current strategies to improve and prolong clinical benefit in ALK driven cancers. Most patients with ALK-driven cancer are sensitive to tyrosine kinase inhibitor (TKI) therapy, but resistance invariably develops. This book discusses topics such as structure and function of ALK, ALK rearranged lung cancer, resistance mechanisms to ALK TKI tumors, and novel therapeutic strategies to enhance crizotinib anti-tumor efficacy in ALCL. Additionally, it encompasses information on drug combinations to enhance ALK TKI anti-tumor efficacy in neuroblastoma and future perspectives in the field. This book is a valuable resource for cancer researchers, clinicians and several members of biomedical field who need to understand more about how to fight ALK resistance in cancer treatment. Explains the biology of ALK RTK, focusing on its tissue expression, structure and functionality Presents an overview of current treatments and the benefits of ALK TKI in lung and other cancer types, such as ALCL, neuroblastoma and inflammatory myofibroblastic tumor Encompasses information on systemic treatments other than TKI, including chemotherapy, immunotherapy and antiangiogenic agents in ALK-driven NSCLC

Download or read book Mechanisms of Drug Resistance in Cancer Therapy written by Mario Mandalà and published by Springer. This book was released on 2019-01-10 with total page 297 pages. Available in PDF, EPUB and Kindle. Book excerpt: A major objective of this book is to reveal unprecedented opportunities to understand and overcome drug resistance through the clinical assessment of rational therapeutic drug combinations and the use of predictive and prognostic biomarkers to enable patient stratification and tailor treatments. It offers to the readers an updated overview on the possible reasons of failure of new and promising therapeutic opportunities.

Download or read book Targeted Therapies in Lung Cancer Management Strategies for Nurses and Practitioners written by Marianne Davies and published by Springer. This book was released on 2019-07-16 with total page 120 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Resistance Mechanisms to ALK Tyrosine Kinase Inhibitors TKIs in NSCLC written by Gonzalo Recondo and published by . This book was released on 2019 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The molecular study and classification of lung adenocarcinomas has led to the development of selective targeted therapies aiming to improve disease control and survival in patients. The anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor from the insulin tyrosine kinase receptor family, with a physiologic role in neural development. Gene rearrangements involving the ALK kinase domain occur in ~3-6% of patients with lung adenocarcinoma. The fusion protein dimerizes leading to transactivation of the ALK kinase domain in a ligand-independent and constitutive manner. Lorlatinib is a third generation ALK inhibitor with high potency and selectivity for this kinase in vitro and in vivo, and elevated penetrance in the central nervous system. Lorlatinib can overcome resistance mediated by over 16 secondary kinase domain mutations occurring in 13 residues upon progression to first - and second - generation ALK TKI. In addition, treatment with lorlatinib is effective for patients who have been previously treated with a first and a second generation or a second generation ALK TKI upfront and is currently approved for this indication. The full spectrum of biological mechanisms driving lorlatinib resistance in patients remains to be elucidated. It has been recently reported that the sequential acquisition of two or more mutations in the kinase domain, also referred as compound mutations, is responsible for disease progression in about 35% of patients treated with lorlatinib, mainly by impairing its binding to the ALK kinase domain. However, the effect of these compound mutations on the sensitivity to the repertoire of ALK inhibitors can vary, and other resistance mechanisms occurring in most patients are unknown. My PhD thesis aimed at exploring resistance to lorlatinib in patients with ALK-rearranged lung cancer through spatial and temporal tumor biopsies and development of patient-derived models. Within the institutional MATCH-R study (NCT02517892), we performed high-throughput whole exome, RNA and targeted next-generation sequencing, together with plasma sequencing to identify putative genomic and bypass mechanisms of resistance. We developed patient-derived cell lines and characterized novel mechanisms of resistance and personalized treatment strategies in vitro and in vivo. We characterized three mechanisms of resistance in four patients with paired biopsies. We studied the induction of epithelial-mesenchymal transition (EMT) by SRC activation in a patient-derived cell line exposed to lorlatinib. Mesenchymal cells were sensitive to combined SRC and ALK co-inhibition, showing that even in the presence of an aggressive and challenging phenotype, combination strategies can overcome ALK resistance. We identified two novel ALK kinase domain compound mutations, F1174L/G1202R, C1156Y/G1269A, occurring in two patients treated with lorlatinib. We developed Ba/F3 cell models harboring single and compound mutations to study the differential effect of these mutations on lorlatinib resistance. Finally, we characterized a novel mechanism of resistance caused by NF2 loss of function at the time of lorlatinib progression through the development of patients derived PDX and cell lines, and in vitro validation of NF2 knock-out with CRISPR/CAS9 gene editing. Downstream activation of mTOR was found to drive lorlatinib resistance by NF2 loss of function and was overcome by providing treatment with mTOR inhibitors.This study shows that mechanisms of resistance to lorlatinib are more diverse and complex than anticipated. Our findings also emphasize how longitudinal studies of tumor dynamics allow deciphering TKI resistance and identifying reversing strategies.

Download or read book Central Nervous System Metastases written by Manmeet Ahluwalia and published by Springer Nature. This book was released on 2019-11-05 with total page 421 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Handbook of Brain Tumor Chemotherapy Molecular Therapeutics and Immunotherapy written by Herbert B. Newton and published by Academic Press. This book was released on 2018-03-28 with total page 848 pages. Available in PDF, EPUB and Kindle. Book excerpt: Handbook of Brain Tumor Chemotherapy, Molecular Therapeutics, and Immunotherapy, Second Edition, provides a comprehensive overview of the molecular methodologies in the neuro-oncology field. There have been profound changes in the landscape of approaches to brain tumor therapy since the first edition—mainly in the areas of molecular biology and molecular therapeutics, as well as in the maturation of immunotherapy approaches (e.g., vaccines). This updated edition has a new, primary focus on multidisciplinary molecular methods, and is broadened to include the latest cutting-edge molecular biology, therapeutics, immunobiology and immunotherapy approaches. As the first comprehensive book to address the molecular research into these concepts, users will find it to be an invaluable resource on the topics discussed. Provides the most up-to-date information regarding conventional forms of cytotoxic chemotherapy, as well as the basic science and clinical application of molecular therapeutics for the treatment of brain tumors Broadly appeals to anyone interested in neuro-oncology and the treatment of brain tumors Features updated chapters on molecular biology, molecular therapeutics, maturation of immunotherapy approaches, and a focus on multidisciplinary molecular methods Includes a new section on the basic science of immunology, as well as thorough updates on the use of vaccine technology and immunotherapy for the treatment of brain tumors

Download or read book Protein Kinase Inhibitors as Sensitizing Agents for Chemotherapy written by and published by Academic Press. This book was released on 2018-11-21 with total page 292 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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

Download or read book Molecular Pathology of Lung Cancer written by Philip T. Cagle and published by Springer Science & Business Media. This book was released on 2012-06-14 with total page 217 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book International Ethical Guidelines for Biomedical Research Involving Human Subjects written by Council for International Organizations of Medical Sciences and published by World Health Organization. This book was released on 2002 with total page 116 pages. Available in PDF, EPUB and Kindle. Book excerpt: The present text is the revised/updated version of the CIOMS International Ethical Guidelines for Biomedical Research Involving Human Subjects. It consists of 21 guidelines with commentaries. A prefatory section outlines the historical background and the revision process and includes an introduction an account of earlier instruments and guidelines a statement of ethical principles and a preamble. An Appendix lists the items to be included in the research protocol to be submitted for scientific and ethical review and clearance. The Guidelines relate mainly to ethical justification and scientific validity of research; ethical review; informed consent; vulnerability - of individuals groups communities and populations; women as research subjects; equity regarding burdens and benefits; choice of control in clinical trials; confidentiality; compensation for injury; strengthening of national or local capacity for ethical review; and obligations of sponsors to provide health-care services. They are designed to be of use to countries in defining national policies on the ethics of biomedical research involving human subjects applying ethical standards in local circumstances and establishing or improving ethical review mechanisms. A particular aim is to reflect the conditions and the needs of low-resource countries and the implications for multinational or transnational research in which they may be partners.

Download or read book Patient Derived Tumor Xenograft Models written by Rajesh Uthamanthil and published by Academic Press. This book was released on 2016-10-13 with total page 488 pages. Available in PDF, EPUB and Kindle. Book excerpt: Patient Derived Tumor Xenograft Models: Promise, Potential and Practice offers guidance on how to conduct PDX modeling and trials, including how to know when these models are appropriate for use, and how the data should be interpreted through the selection of immunodeficient strains. In addition, proper methodologies suitable for growing different type of tumors, acquisition of pathology, genomic and other data about the tumor, potential pitfalls, and confounding background pathologies that occur in these models are also included, as is a discussion of the facilities and infrastructure required to operate a PDX laboratory. Offers guidance on data interpretation and regulatory aspects Provides useful techniques and strategies for working with PDX models Includes practical tools and potential pitfalls for best practices Compiles all knowledge of PDX models research in one resource Presents the results of first ever global survey on standards of PDX development and usage in academia and industry

Download or read book Targeted Therapies for Lung Cancer written by Ravi Salgia and published by Springer. This book was released on 2019-06-26 with total page 238 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Preclinical Modeling of Driver Alterations in Non small Cell Lung Cancer written by Ruoshi Shi and published by . This book was released on 2019 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Non-small cell lung cancer (NSCLC) is the leading cause of cancer related mortality and accounts for more than 1.6 million deaths worldwide each year. In the past decade, therapeutic treatments for NSCLC have extended beyond surgery and standard chemotherapies. These advancements have largely focused on the identification of oncogenic drivers and assessment of their ability to predict response to targeted therapy. Despite these advancements, the lack of initial response to single agent treatment and acquired drug resistance are recurring issues that arise in NSCLC. Additionally, preclinical models such as cell lines have been widely used for drug testing and understanding disease pathogenesis. However, they have molecularly deviated from patient tumors and may not accurately reflect drug response in patients. Thus, there is an unmet need to develop clinically and biologically relevant models of NSCLC. These models may then be used to identify new therapeutic strategies to overcome acquired resistance and improve single agent therapy response with combination therapy targeting the major drivers of this disease. In this dissertation, I have modeled several oncogenic drivers of NSCLC to identify novel treatment strategies using patient-derived xenografts (PDX) and organoids. In the first study, I have determined absence of ALK protein by IHC as a primary resistance mechanism and MET amplification and BRAF mutation as secondary resistance mechanisms to ALK inhibitors in lung adenocarcinoma. In the second study, I have identified CDK4/6 inhibitors as promising agents to use in combination with PI3K inhibitors in PIK3CA mutant lung squamous cell carcinoma (LUSC). In the third study, I have developed a protocol for culturing NSCLC organoids and identified FGFR1 and MEK inhibitor combination as a potential therapeutic strategy in FGFR1 amplified LUSC. The findings outlined in this dissertation will not only describe additional preclinical models, but also therapeutic approaches to overcome acquired drug resistance and improve response to single agent therapy with potential drug combinations in NSCLC.

Download or read book Targeting Cellular Signalling Pathways in Lung Diseases written by Kamal Dua and published by Springer Nature. This book was released on 2021-07-02 with total page 926 pages. Available in PDF, EPUB and Kindle. Book excerpt: The book comprehensively reviews and provides detailed insight into the cellular and molecular signalling mechanisms involved in pathophysiology of various respiratory diseases, towards developing effective therapeutic strategies in the management and treatment of lung disease. It also covers promising advances in the field of therapeutics that could lead to novel clinical therapies capable of preventing or reversing the disease features including novel strategies for targeting chronic lung diseases using advanced drug delivery systems. Importantly, the book examines the significance and relevance of the plant extracts and their constituents with therapeutic efficiencies against lung diseases. As such, the book offers a blend of translational, biological, chemical, and drug delivery aspects relevant to respiratory diseases, thus, offering a valuable resource for pulmonologists and translational researchers working in the field of pulmonary biology and respiratory medicine.

Download or read book Lung Cancer A Practical Approach to Evidence Based Clinical Evaluation and Management written by Lynn T. Tanoue and published by Elsevier Health Sciences. This book was released on 2018-05-30 with total page 350 pages. Available in PDF, EPUB and Kindle. Book excerpt: Get a quick, expert overview of the many key facets of lung cancer evaluation and management with this concise, practical resource by Drs. Lynn T. Tanoue and Frank Detterbeck. This easy-to-read reference presents a summary of today’s best evidence-based approaches to diagnosis and management in this critical area. Covers diagnosis and evaluation, treatment considerations, and comprehensive care options for patients with lung cancer. Provides insight on evidence for today’s best practices, as well as future directions in the field. Consolidates today’s evidence-based information on the clinical aspects of lung cancer into one convenient resource.

Download or read book Heat Shock Proteins in Cancer written by Stuart K. Calderwood and published by Springer Science & Business Media. This book was released on 2007-09-09 with total page 399 pages. Available in PDF, EPUB and Kindle. Book excerpt: Heat shock proteins are emerging as important molecules in the development of cancer and as key targets in cancer therapy. These proteins enhance the growth of cancer cells and protect tumors from treatments such as drugs or surgery. However, new drugs have recently been developed particularly those targeting heat shock protein 90. As heat shock protein 90 functions to stabilize many of the oncogenes and growth promoting proteins in cancer cells, such drugs have broad specificity in many types of cancer cell and offer the possibility of evading the development of resistance through point mutation or use of compensatory pathways. Heat shock proteins have a further property that makes them tempting targets in cancer immunotherapy. These proteins have the ability to induce an inflammatory response when released in tumors and to carry tumor antigens to antigen presenting cells. They have thus become important components of anticancer vaccines. Overall, heat shock proteins are important new targets in molecular cancer therapy and can be approached in a number of contrasting approaches to therapy.

Download or read book Pulmonary Adenocarcinoma Approaches to Treatment written by Leora Horn and published by Elsevier Health Sciences. This book was released on 2018-10-24 with total page 400 pages. Available in PDF, EPUB and Kindle. Book excerpt: Get a quick, expert overview of the latest treatment and management approaches for adenocarcinoma of the lung, including novel therapeutics in immunotherapy and targeted therapies. This practical title, edited by Dr. Leora Horn, offers succinct coverage of clinically-focused topics and guidelines, making it an ideal resource for practicing and trainee oncologists and other members of the cancer care team.

Download or read book Adverse Events and Oncotargeted Kinase Inhibitors written by Giuseppe Tridente and published by Academic Press. This book was released on 2017-05-08 with total page 738 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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