Author: Jacinta SimasiPublisher:
ISBN:
Category :
Languages : en
Pages : 256
Book Description
Mechanisms of Acquired Resistance to Tyrosine Kinase Inhibitors in Lung Cancer
Author: Jacinta SimasiPrimary and Acquired Resistance in Lung Cancer
Author: Rossella BrunoPublisher: Frontiers Media SA
ISBN: 2832539394
Category : Medical
Languages : en
Pages : 116
Book Description
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.
Acquired Resistance to Targeted Therapy in EGFR-mutant Lung Adenocarcinoma
Author: Caroline Amalia NebhanPublisher:
ISBN:
Category : Electronic dissertations
Languages : en
Pages : 145
Book Description
Exploring the Use of Tyrosine Kinase Inhibitors in Glioblastoma and RET-rearranged Lung Cancer to Curtail Cell Migration and Invasion and Improve Therapy by Understanding Drug Resistance
Author: Sarah K. NelsonPublisher:
ISBN:
Category :
Languages : en
Pages : 164
Book Description
The exponential increase in targeted tyrosine kinase inhibitor (TKI) therapies approved for use in cancer or in late-stage clinical trials has revolutionized the treatment of solid tumors over the last decade. However, many questions regarding the fundamental biology of oncogenic and wild-type receptor tyrosine kinases (RTKs) and how cancer cells adapt to become resistant to TKI therapies have been raised. This work addresses some of these questions specifically as they relate to glioblastoma (GBM) and RET fusion positive lung adenocarcinoma (LAC). First, I demonstrate the feasibility of targeting the Mer receptor tyrosine kinase (MERTK) in order to decrease glioblastoma cell migration and invasion. Using genetic knockdown and the MERTK TKIs foretinib and UNC2025, I demonstrate that MERTK inhibition decreases the migration and invasion of glioblastoma cells in two- and three dimensional in vitro assay systems. Further, I demonstrate that siRNA knockdown of MERTK inhibits expression of focal adhesion kinase (FAK), a master regulator of cell migration and invasion. Second, I demonstrate that mechanisms of acquired resistance to the RET-inhibitor ponatinib RET positive LAC result in reactivation of RAS/MAPK signaling either through the acquisition of oncogenic NRAS p.Q61K signaling or through increased dependence upon wild-type EGFR and AXL signaling. And third, I investigate the mechanisms through which combination mTOR and RET inhibition is improving patient responses to targeted therapy in RET positive LAC patients and demonstrate that while RET inhibition partially suppresses signaling through mTOR, maximal inhibition of this signaling pathway is not achieved without the addition of mTOR inhibition with everolimus. Overall, these pre-clinical studies indicate that clinically available targeted therapies can be used to enhance the inhibition of the glioblastoma cell migration and invasion, as well as to target intrinsic and acquired resistance to targeted RET inhibition in RET fusion positive glioblastoma.
Resistance to Tyrosine Kinase Inhibitors
Author: Daniele FocosiPublisher: Springer
ISBN: 3319460919
Category : Medical
Languages : en
Pages : 194
Book Description
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.
Molecular Pathology of Lung Cancer
Author: Philip T. CaglePublisher: Springer Science & Business Media
ISBN: 1461431972
Category : Medical
Languages : en
Pages : 217
Book Description
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.
Targeted Therapies in Lung Cancer: Management Strategies for Nurses and Practitioners
Author: Marianne DaviesPublisher: Springer
ISBN: 3030165507
Category : Medical
Languages : en
Pages : 120
Book Description
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.
Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non-small Cell Lung Cancer
Author: Novel Mechanisms of Resistance to EGFR Inhibitory Drugs in Non-small Cell Lung Cancer
Author: Mechanisms of Drug Resistance in Cancer Therapy
Author: Mario MandalàPublisher: Springer
ISBN: 3030105075
Category : Medical
Languages : en
Pages : 297
Book Description
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.