Download or read book Acquired Resistance to Targeted Therapy in EGFR mutant Lung Adenocarcinoma written by Caroline Amalia Nebhan and published by . This book was released on 2014 with total page 145 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Overcoming Resistance to EGFR Inhibitors in EGFR Mutant NSCLC written by Anthony Faber and published by Academic Press. This book was released on 2023-01-30 with total page 150 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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
Download or read book Primary and Acquired Resistance in Lung Cancer written by Rossella Bruno and published by Frontiers Media SA. This book was released on 2023-11-23 with total page 116 pages. Available in PDF, EPUB and Kindle. Book excerpt: Lung cancer is one of the leading causes of cancer-related death worldwide with a prevalence of advanced stage in up to 70% of cases and a five-year survival reached in only 5-10% of cases. Targeted therapies and immunotherapy have greatly improved the management of patients with advanced non-small cell lung cancer (NSCLC), particularly adenocarcinoma, and current diagnostic algorithms are based on the molecular analysis of several biomarkers necessary to tailor therapy. In detail, patients harboring sensitive driver alterations within the oncogenes EGFR, BRAF, ALK, ROS1, RET and NTRK1/2/3 can be treated with approved kinase inhibitors (KIs). In addition, drugs against MET, KRAS G12C and other markers are providing interesting results across different clinical trials. Targeted therapies have greatly improved therapeutic options for NSCLC, but resistance inevitably occurs usually after one year of treatment and some patients, although harboring sensitive alterations, never respond to treatment.
Download or read book Successes and Limitations of Targeted Cancer Therapy written by S. Peters and published by Karger Medical and Scientific Publishers. This book was released on 2014-02-19 with total page 126 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book EGFR Directed Therapy in Lung Cancer written by So Yeon Kim and published by Cambridge University Press. This book was released on 2023-01-26 with total page 72 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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).
Download or read book Guide to Targeted Therapies EGFR mutations in NSCLC written by Federico Cappuzzo and published by Springer. This book was released on 2014-09-25 with total page 75 pages. Available in PDF, EPUB and Kindle. Book excerpt: Guide to Targeted Therapies: EGFR Mutations in NSCLC is a speedy and up-to-date review, which discusses EGFR mutations, 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 EGFR gene mutations as well as a summary of current therapies will benefit from this succinct guide.
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 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 122 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 Study of Molecular Mechanisms of Sensitivity and Resistance to EGFR Targeted Therapy in Lung Cancer written by Zhenfeng Zhang and published by . This book was released on 2010 with total page 143 pages. Available in PDF, EPUB and Kindle. Book excerpt: Lung cancer is still the leading cause of cancer-related death worldwide. EGFR-targeted tyrosine kinase inhibitors (TKI), such as erlotinib and gefitinib, have dramatic clinical effects on EGFR-dependent lung cancers and are used as first-line therapy for patients with EGFR-mutant lung tumors. However, eventually all tumors acquire secondary resistance to the drugs and progress. Sensitivity to such EGFR-TKI is determined by activating mutations in EGFR tyrosine kinase domain whereas resistance to the TKI can be conferred by EGFR secondary mutations such as EGFR T790M and MET activation. Using a T790M-mutant H1975 NSCLC cell line which is gefitinib-resistant but sensitive to an irreversible EGFR inhibitor CL-387,785 allowed us to compare the target gene changes by treatment with gefitinib or CL387,785 in a transcriptional profiling study. We identified several dual specificity phosphatases (DUSPs) among the most highly and immediately regulated genes upon EGFR inhibition. DUSPs act as natural terminators of MAPK signal transduction and we demonstrate a tumor suppressive role of DUSP6 via targeting ERK activity. We also show that the regulation of DUSP6 is mediated at the promoter level by ETS1, a well-known nuclear target of activated ERK, indicating an important negative feedback loop in NSCLC. Furthermore, we developed an erlotinib-resistant NSCLC cell model and explored mechanisms of such resistance. We discover a novel mechanism of erlotinib resistance involving overexpression of AXL. Further studies confirm that co-treatment using erlotinib along with AXL knockdown or pharmacological inhibition resensitizes these resistant cells leading to cell death. These results suggest that an oncogenic switch from EGFR-dependent to EGFR/AXL-codependent signaling can lead to secondary EGFR-TKI resistance in NSCLC. In summary, our findings provide novel options for the improved targeting of EGFR-dependent tumors by the identification of DUSP6 and AXL as important modulators of EGFR sensitivity/resistance.
Download or read book Guide to Targeted Therapies Treatment Resistance in Lung Cancer written by Federico Cappuzzo and published by Springer. This book was released on 2015-10-15 with total page 71 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Current Applications for Overcoming Resistance to Targeted Therapies written by Myron R. Szewczuk and published by Springer. This book was released on 2019-07-15 with total page 328 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
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 244 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 Cancer Signaling written by Christoph Wagener and published by John Wiley & Sons. This book was released on 2016-08-12 with total page 357 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cancer, which has become the second-most prevalent health issue globally, is essentially a malfunction of cell signaling. Understanding how the intricate signaling networks of cells and tissues allow cancer to thrive - and how they can be turned into potent weapons against it - is the key to managing cancer in the clinic and improving the outcome of cancer therapies. In their ground-breaking textbook, the authors provide a compelling story of how cancer works on the molecular level, and how targeted therapies using kinase inhibitors and other modulators of signaling pathways can contain and eventually cure it. The first part of the book gives an introduction into the cell and molecular biology of cancer, focusing on the key mechanisms of cancer formation. The second part of the book introduces the main signaling transduction mechanisms responsible for carcinogenesis and compares their function in healthy versus cancer cells. In contrast to the complexity of its topic, the text is easy to read. 32 specially prepared teaching videos on key concepts and pathways in cancer signaling are available online for users of the print edition and have been integrated into the text in the enhanced e-book edition.
Download or read book Second Line Treatment of Non Small Cell Lung Cancer Clinical Pathological and Molecular Aspects of Novel Promising Drugs written by Umberto Malapelle and published by Frontiers Media SA. This book was released on 2017-08-29 with total page 86 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Therapeutic Strategies in EGFR Mutant Lung Cancer written by Yaxiong Zhang and published by Frontiers Media SA. This book was released on 2022-11-03 with total page 239 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book MET EGFR Dimerisation in Lung Adenocarcinoma is Dependent on EGFR Mutations and Altered by MET Kinase Inhibition written by Richard Lee and published by . This book was released on 2017 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Prognosis in advanced stage lung cancer is extremely poor with few effective therapies. EGFR tyrosine kinase inhibitors (TKIs) have high response rates in patients with activating EGFR mutations and are now an established part of therapy in selected patients. Such advances herald a previously unprecedented enthusiasm for the possibilities of targeted therapy. Acquired resistance however is widespread - the EGFR T790M mutation in particular represents approximately 50% of these. MET amplification is also an important route of resistance and preclinical data suggests synergy between therapies targeting these two receptors. We hypothesized that EGFR mutation status determines the EGFR-MET interaction and response to MET inhibition. We tested this hypothesis by using cells derived from NCI-H1975, which possess L858R and T790M EGFR mutations. This cell model and a derived murine xenograft experiment provided a platform with which to test these ideas by using assays of tumorigenicity in vitro; tumour growth/stroma formation in vivo and a selective MET kinase inhibitor, SGX523. EGFR-MET interaction was assessed by a Förster Resonance Energy Transfer (FRET) Fluorescence Lifetime Imaging Microscopy (FLIM) assay developed as part of this thesis that quantified EGFR-MET dimer formation. SGX523 significantly reduced cell proliferation, xenograft tumour growth and ERK phosphorylation in the presence of the EGFR L858R-T790M mutations but not with EGFR L858R alone where SGX523 reduced stroma formation but not growth. SGX523 reduced EGFR-MET dimerisation in the EGFR L858R-T790M mutant but increased EGFR-MET interaction in the presence of EGFR L858R alone. Little effect was seen with EGFR WT in response to SGX523 for any of these indices. This thesis provides novel data for the mechanistic understanding of EGFR-MET heterodimerisation and the accompanying discussion explores how this is relevant for EGFR and MET targeted therapies.
Download or read book Pocket Oncology written by Alexander Drilon and published by Lippincott Williams & Wilkins. This book was released on 2014 with total page 352 pages. Available in PDF, EPUB and Kindle. Book excerpt: Pocket Oncology, developed and edited by oncologists at Memorial Sloan-Kettering Cancer Center, is a simple, yet comprehensive, review of basic principles of cancer management. Prepared in the style and format of books in the popular Pocket Notebook series, Pocket Oncology is intended as a quick reference presented in easy to read bulleted text, and using diagrams and charts where appropriate. Each oncologic disease is presented on two facing pages that review initial clinical presentation, pathophysiology, staging, current standard of care treatments, and active areas of current research. Edited by Alexander Drilon and Michael Postow, the content of the book has been written by medical oncology fellows and each disease entity has been authoritatively reviewed by an oncologist with specific expertise in each subspecialty of oncology. Features: -simple, comprehensive, review of basic principles of oncology in easy to read bulleted text, using diagrams and charts where appropriate. -its small size makes it easy to carry the pocket of a lab coat for quick reference to information while in the hospital or oncology clinic. -perfect for medical students, residents, fellows, physician assistants, and nurses who perform daily oncologic care.
