Overcoming Resistance to EGFR Inhibitors in EGFR-Mutant NSCLC
- 1st Edition, Volume 19 - January 30, 2023
- Imprint: Academic Press
- Editor: Anthony Faber
- Language: English
- Hardback ISBN:9 7 8 - 0 - 1 2 - 8 2 2 8 3 3 - 3
- eBook ISBN:9 7 8 - 0 - 1 2 - 8 2 2 8 3 4 - 0
Overcoming Resistance to EGFR Inhibitors in EGFR Mutant NSCLC presents updated information on how EGFR mutant lung cancers evolve to evade EGFR inhibitors, clinical strategie… Read more
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Request a sales quoteOvercoming 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
Cancer researchers, medical scientists, clinicians, graduate students
- Cover
- Title page
- Table of Contents
- Copyright
- Cover Image Insert
- Aims and Scope for Series “Cancer Sensitizing Agents for Chemotherapy”
- About the Series Editor
- Aims and Scope of the Volume
- About the Volume Editor
- Preface
- Contributors
- Chapter 1: Historical development of EGFR-targeted therapy
- Abstract
- Conflict of interest
- Introduction
- Pan-cancer preclinical studies and phase I trials of EGFR TKIs
- Early phase II/III clinical trials of gefitinib and erlotinib on lung cancer
- EGFR mutations as biomarker of TKI response and approval of EGFR TKIs in EGFR-mutated lung cancer
- Development of second-generation EGFR TKIs
- Development of third-generation EGFR TKIs
- EGFR TKI in early-stage completely resected lung cancer patients
- References
- Chapter 2: The development and implementation of EGFR inhibitors in advanced NSCLC
- Abstract
- Conflict of interest
- Introduction
- A brief overview of EGFR structure and signaling
- First-generation EGFR tyrosine kinase inhibitors
- First-generation EGFR inhibitors in patients with an activating EGFR mutation
- Second-generation EGFR inhibitors
- Third-generation EGFR inhibitors
- Osimertinib in brain metastases of patients with EGFR-mutant NSCLC
- Exon 20 insertions
- Checkpoint inhibitor therapy in patients with EGFR mutations
- Current standard management of EGFR-mutant patients
- Conclusions
- Future directions
- References
- Chapter 3: YAP/TAZ-mediated resistance to EGFR inhibitors
- Abstract
- Conflict of interest
- Acknowledgment
- Introduction
- Regulation of YAP/TAZ through the Hippo pathway-dependent and -independent mechanisms
- The role of YAP/TAZ in human cancer
- Interplay between YAP/TAZ and the EGFR signaling pathway
- The role of YAP/TAZ in resistance to EGFR inhibitors
- Molecular mechanisms of YAP/TAZ-mediated resistance to EGFR inhibitors
- Molecular mechanism of dysregulation of YAP/TAZ in EGFR inhibitor-resistant cells
- Potential combination therapies to overcome YAP-mediated resistance to TKI
- Concluding remarks
- References
- Chapter 4: Role of epithelial to mesenchymal transition in the resistant mechanism of EGFR-TKIs
- Abstract
- Conflict of interest
- Acknowledgment
- Introduction
- Molecular mechanisms of EMT in cancer
- EMT in EGFR-TKI resistance
- Mechanisms of induction of EMT in EGFR-mutant lung cancer
- Strategy to overcome EGFR-TKI resistance induced by EMT
- Conclusion and future perspectives
- References
- Chapter 5: Apoptosis signaling in EGFR inhibitor resistance in NSCLC
- Abstract
- Conflict of interest
- Introduction
- BCL-2 proteins: Regulators of mitochondrial apoptosis signaling
- BCL-2 proteins govern response to EGRF inhibitors in EGFR-mutant NSCLC
- Conclusions and perspectives
- References
- Chapter 6: Control of EGFR signaling by endocytosis and endosomal trafficking
- Abstract
- Conflict of interest
- Acknowledgment
- Overview of EGFR trafficking and signaling
- Endocytosis
- Recycling
- Endosome maturation and lysosomal sorting
- EGFR trafficking and autophagy
- EGFR mutations and membrane trafficking
- Conclusions
- References
- Chapter 7: Epithelial-mesenchymal transition and resistance to EGFR inhibitors
- Abstract
- Conflict of interest
- Basics of epithelial-mesenchymal transition
- What are the key drivers of EMT in anti-EGFR drug resistance?
- EMT emerges as having a prominent role in drug resistance
- Key targets of mesenchymal transcriptional repressors in EMT
- EMT emerges as a resistant mechanism to EGFR inhibitors in EGFR-mutant NSCLC
- Key signaling changes induced by EMT in EGFR-mutant NSCLC
- Acquired resistance to targeted therapies and BCL2 family members
- Cell death and EMT in EGFR inhibitor resistance in EGFR-mutant NSCLC
- Targeting BCL-xL to resensitize to EGFR inhibitors in EMT EGFR-mutant NSCLC
- Conclusions
- References
- Index
- Edition: 1
- Volume: 19
- Published: January 30, 2023
- No. of pages (Hardback): 150
- No. of pages (eBook): 150
- Imprint: Academic Press
- Language: English
- Hardback ISBN: 9780128228333
- eBook ISBN: 9780128228340
AF
Anthony Faber
Dr. Faber’s research program includes studying resistance mechanisms to targeted therapies in lung cancer. During his postdoctoral training, he discovered that low expression levels of functional BIM, a pro-apoptotic protein, was sufficient to impart resistance to EGFR inhibitors in EGFR mutant lung cancer through loss of a cell death response. Loss of functional BIM is now part of clinical decision making for EGFR mutant lung cancer patients and combination therapy of EGFR inhibitors with BH3 mimetics to rescue or improve cell death responses are being explored clinically. Dr. Faber’s laboratory more recently linked epithelial-to-mesenchymal related EGFR inhibitor resistance with low levels of BIM, and a deficient cell death response.
Affiliations and expertise
Co-leader. Developmental therapeutics, Massey Cancer Center, Associate Professor, Virginia Commonwealth University, USARead Overcoming Resistance to EGFR Inhibitors in EGFR-Mutant NSCLC on ScienceDirect