Overcoming Cancers Resistant to HER-2 Antibodies

1st Edition, Volume 2 - July 15, 2024
Editor: Benjamin Bonavida
Language: English
Hardback ISBN:
9 7 8 - 0 - 1 2 - 8 1 6 4 0 8 - 2
eBook ISBN:
9 7 8 - 0 - 1 2 - 8 1 6 7 3 8 - 0

Overcoming Cancers Resistant to HER-2 Antibodies provides general updated information on the resistance of various human cancers to anti-HER2 therapeutic antibodies. The book a… Read more

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Overcoming Cancers Resistant to HER-2 Antibodies provides general updated information on the resistance of various human cancers to anti-HER2 therapeutic antibodies. The book also discusses the description of various sensitizing agents that can reverse resistance when used in combination with anti-HER2 antibodies. There have been a lot of reports in which the treatment with anti-HER2 antibodies for various cancers has resulted in clinical responses; however, there have been also subsets of cancer patients who did not respond initially, and several responding patients developed resistance following treatments. Sections cover Lapatinib, Ganetespib, Paclitaxel, Celecoxib, Emantasine, Liposomal Doxorubicin, and Kinase Inhibitors.

This book is a valuable source for cancer researchers, oncologists, pharmacologists and different members of the biomedical field interested in fighting cancer resistance to HER-2 antibodies.

Cover image
Title page
Table of Contents
Front Matter
Copyright
Aims and scope of series “Breaking tolerance to antibody-targeted therapies”
About the Series Editor
Aims and scope of the volume “Overcoming Cancers Resistant to HER-2 Antibodies”
Preface “Overcoming Cancers Resistant to HER-2 Antibodies”
Contributors
Chapter 1 Resistance of breast cancer brain metastasis to trastuzumab therapy
Abstract
Conflict of interest
Introduction
Trastuzumab mechanism of action
Notable mechanisms of HER2+ BCBM resistance to trastuzumab
Emerging therapeutics for treatment of HER2+ BCBM
Emerging strategies for crossing the blood-tumor barrier in trastuzumab-resistant BCBM
Overview and efficacy of trastuzumab combination therapy
Active clinical trials investigating brain metastases in HER2+ BC
Conclusion
References
Chapter 2 Resistance of HER2-expressing breast cancer patients treated with trastuzumab: Underlying mechanisms of resistance and reversals
Abstract
Introduction
Treatment options for breast cancer
General features of HER2
Treatment of HER2-expressing breast cancer
Trastuzumab
Mechanisms of resistance to trastuzumab treatment
Trastuzumab-drug conjugates to overcome trastuzumab resistance
Remarks and perspectives
References
Chapter 3 Understanding mechanisms of resistance to HER2-targeted therapies in HER2-positive breast cancer
Abstract
Conflict of interest
Introduction
HER2-targeted therapeutic effector mechanisms
Resistance mechanisms to HER2-targeted therapies
Conclusions
References
Chapter 4 Clinical implications and management strategies of resistance to anti-HER2 antibodies in breast cancer
Abstract
Conflict of interest
Introduction
HER2 signaling in MBC and targeted therapy
Tackling HER2-positive MBC with targeted therapies and improved survival
Emerging pathways of anti-HER2 therapy insensitivity and new therapeutic targets
Anti-HER2 therapy resistance with clinical challenge and management strategies
Future prospects
Conclusion
References
Chapter 5 Overexpression of antiapoptotic gene products and resistance to trastuzumab treatment of breast cancer
Abstract
Introduction
Breast cancer resistances to conventional treatments
HER2 overexpression and signaling
The anti-HER2 mAb trastuzumab
General trastuzumab resistance mechanisms
Trastuzumab and antiapoptotic proteins
Targeting antiapoptotic gene products to restore response to trastuzumab
Combination of trastuzumab with anticancer immunotherapy
Conclusions and future perspectives
References
Chapter 6 How does understanding epigenetics help circumvent HER-2 antibody resistance?
Abstract
Conflict of interest
Introduction
Molecular target therapy and anti-HER2 antibody mechanism of action and their combinations with other antineoplastic drugs
Epigenetics and resistance to treatments: Mechanistic detailing
Therapeutic antibodies and main clinical trials
Impact on immune response and cell cycle
Perspectives
Conclusion
References
Chapter 7 Resistance of HER2-expressing ovarian cancer to trastuzumab and mechanisms of overcoming resistance
Abstract
Introduction
HER overview/HER2 expression
Mechanisms of HER2 overexpression in cancer
Activation of signaling pathways by HER2 overexpression and associated consequences
Trastuzumab treatment of ovarian cancer
Mechanisms of resistance
Overcoming resistance to trastuzumab
Discussion and future perspectives
References
Chapter 8 Clinical implications of resistance to anti-HER2 antibodies in breast cancer
Abstract
Conflict of interest
Introduction
Resistance to anti-HER2 monotherapies
Impaired interaction of trastuzumab to HER2
Lapatinib
Trastuzumab-Emtansine drug conjugate
Trastuzumab and Lapatinib combination
Trastuzumab plus Pertuzumab
Conclusion
References
Chapter 9 Highlights of current and future for the treatment of resistant HER2+ breast cancer to HER2-targeted therapies
Abstract
Introduction
New therapeutic approaches to overcome resistance
Harnessing the immune system
Concluding remarks
References
Index

Benjamin Bonavida

Dr. Benjamin Bonavida is currently a Distinguished Research Professor at the University of California, Los Angeles (UCLA). He is affiliated with the Department of Microbiology, Immunology and Molecular Genetics, UCLA David Geffen School of Medicine, and the Jonsson Comprehensive Cancer Center at UCLA. His research career, thus far, has focused on investigations in the fields of basic immunochemistry and cancer immunobiology. His research investigations have ranged from the biochemical, molecular, and genetic mechanisms of cell-mediated killing and tumor cell resistance to chemo-immuno cytotoxic drugs. The reversal of tumor cell resistance was investigated by the use of various selected sensitizing agents based on molecular mechanisms of resistance. In these investigations, there was the newly characterized dysregulated NF-kB/ Snail/YY1/RKIP/PTEN loop in many cancers that was reported to regulate cell survival, proliferation, invasion, metastasis, and resistance. Emphasis was focused on the roles of the tumor suppressor Raf kinase inhibitor protein (RKIP) and the tumor promoter Yin Yang 1 (YY1) and the role of nitric oxide (NO) as a chemo-immuno-sensitizing factor. Many of the aforementioned studies are centered on the clinical challenging features of cancer patients’ failure to respond to both conventional and targeted therapies. Dr. Bonavida has been active in the organization of regular sequential international miniconferences that are highly focused on the roles of YY1, RKIP, and nitric oxide in cancer and their potential therapeutic applications. Several books edited or coedited have been published. In addition, he is the Series Editor of books (over 20) published by Springer/Nature: Resistance to Anti-Cancer Targeted Therapeutics. In addition, he is presently the Series Editor of Three Series published by Elsevier/Academic Press on “Cancer Sensitizing Agents for Chemotherapy,” “Sensitizing Agents for Cancer Resistance to Cell Mediated Immunotherapy,” and “Breaking Tolerance to Anti-Cancer Antibody Immunotherapy.” He is the Editor-in-Chief of the Journal Critical Reviews in Oncogenesis, Editor-in-Chief of Onco Therapeutics, and Associate Editor of “Critical Reviews in Immunology.” Dr. Bonavida has published over 500 research publications and reviews in various scientific journals of high impact.

Affiliations and expertise

Distinguished Research Professor, Department of Microbiology, Immunology and Molecular Genetics, David Ge en School of Medicine, Jonsson Comprehensive Cancer Center, University of California at Los Angeles, California, USA

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Overcoming Cancers Resistant to HER-2 Antibodies

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Benjamin Bonavida