Novel Sensitizing Agents for Therapeutic Anti-EGFR Antibodies

Novel Sensitizing Agents for Therapeutic Anti-EGFR Antibodies

1st Edition - August 1, 2022

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  • Editor: Shi Hu
  • Hardcover ISBN: 9780128215845

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Description

Novel Sensitizing Agents for Therapeutic Anti-EGFR Antibodies presents a description of the sensitizers used to overcome resistance to anti-EGFR targeted antibody therapies in cancer, including novel engineered antibody drugs and other sensitizers. The book gives insights into the landscape of anti-EGFR based cancer treatments, the challenges of targeted therapy, and a glimpse into the future of antibody therapy. It offers pertinent science information on strategies used for the rational design and discovery of novel sensitizing agents, and in addition, translational studies involving pre-clinical and clinical design. This book is an indispensable resource for cancer researchers, medicinal chemists and other biomedical scientists.Finally, the book covers basic science strategies used in drug discovery and preclinical evaluation focused on EGFR blockage resistance, as well as clinical trial methodology, including clinical pharmacokinetics and imaging to address issues of efficacy evaluation of the new anticancer sensitizers for anti-EGFR drug resistance.

Key Features

  • Presents detailed descriptions on the history, chemistry, mechanism of action, structure-function relationships, pharmacology, side effects, dosing and formulation of new sensitizers to anti-EGFR antibodies
  • Provides molecular structures for all novel anticancer drugs, along with strategies to overcome resistance to anti-EGFR antibodies
  • Encompasses up-to-date information on the cancer drug discovery process, including new research tools, tumor-targeting strategies, and fundamental concepts in emerging areas of precision medicine

Readership

Cancer researchers, medical scientists, clinicians, graduate students, pharmacologists

Table of Contents

  • 1. Introduction: Overview of anti-EGFR antibody therapy in cancer
    2. Molecular Mechanisms of Resistance to therapeutic antibodies to the Epidermal Growth Factor Receptor

    Part I: 1 ERBB inhibitors as sensitizers for anti-EGFR antibodies
    3. MM-151 overcomes acquired resistance to cetuximab and panitumumab in colorectal cancers harboring EGFR extracellular domain mutations
    4. Sym004 Anti-EGFR Antibody Mixture overcomes resistance to anti-EGFR antibodies in Metastatic Colorectal Cancer
    5. HER3 Targeting with MM-121 Sensitizes HNSCC to Cetuximab by Reducing HER3 Activity and HER2/HER3 Dimerization
    6. Pan-HER, an Antibody Mixture Simultaneously Targeting EGFR, HER2, and HER3, Effectively Overcomes resistance to anti-EGFR antibodies.
    7. Pan-HER targeting with Four-in-one antibodies disrupting the HER/MET crosstalk
    8. Overcoming acquired resistance to cetuximab by combined EGFR and HER3 neutralizing monoclonal antibodies
    9. Dual targeting of EGFR and HER3 with MEHD7945A overcomes acquired resistance to EGFR inhibitors
    10. Inhibition of ERBB2 signaling overcome resistance to the EGFR-directed therapeutic antibody cetuximab
    11. Dual inhibition of EGFR with afatinib and cetuximab in kinase inhibitor-resistant EGFR models

    Part II: Alternative receptor tyrosine kinase inhibitors as sensitizers for anti-EGFR antibodies
    12. BET Inhibition Overcomes Receptor Tyrosine Kinase-Mediated Cetuximab Resistance in HNSCC
    13. Dual Inhibition of EGFR and c-Src by Cetuximab and Dasatinib Combined with FOLFOX Chemotherapy in Patients with Metastatic Colorectal Cancer
    14. A Novel Bispecific Antibody Targeting EGFR and cMet Is Effective against EGFR Inhibitor-Resistant Lung Tumors
    15. Use MET kinase inhibitor to overcome cetuximab resistance in CRC
    16. EGFR- and VEGF(R)-targeted small molecules show synergistic activity in colorectal cancer models refractory to combinations of monoclonal antibodies
    17. Antitumor activity of ZD6474, a vascular endothelial growth factor receptor tyrosine kinase inhibitor, in human cancer cells with acquired resistance to anti epidermal growth factor receptor therapy

    Part III: Downstream kinase inhibitors as sensitizers for anti-EGFR antibodies
    18. Antibody-mediated delivery of anti-KRAS-siRNA in vivo overcomes therapy resistance in colon cancer
    19. Primary and acquired resistance of colorectal cancer cells to anti-EGFR antibodies converge on MEK/ERK pathway activation and can be overcome by combined MEK/EGFR inhibition
    20. MEK1/2 inhibitors may be potential therapies for colorectal cancer that is resistant to EGFR monoclonal antibody therapy
    21. EGFR/JIP-4/JNK2 signaling attenuates cetuximab-mediated radiosensitization of squamous cell carcinoma cells
    22. Efficient blockade of Akt signaling is a determinant factor to overcome resistance to matuzumab.

    Part IV: Other sensitizers for anti-EGFR antibodies
    23. Inhibition of SLC1A5 sensitizes colorectal cancer to cetuximab
    24. Targeting of PYK2 Synergizes with EGFR Antagonists in Basal-like TNBC and Circumvents HER3-Associated Resistance via the NEDD4-NDRG1 Axis
    25. Targeting EGFR/Notch to overcome resistance to anti-EGFR antibodies
    26. Hedgehog signaling alters reliance on EGF receptor signaling and mediates anti-EGFR therapeutic resistance in head and neck cancer
    27. Novel toll-like receptor 9 agonist induces epidermal growth factor receptor (EGFR) inhibition and synergistic antitumor activity with EGFR inhibitors
    28. Rationale for combination of therapeutic antibodies targeting tumor cells and immune checkpoint receptors

Product details

  • No. of pages: 300
  • Language: English
  • Copyright: © Academic Press 2022
  • Published: August 1, 2022
  • Imprint: Academic Press
  • Hardcover ISBN: 9780128215845

About the Editor

Shi Hu

Dr. Shi Hu received an MD and a PhD in tumor immunology from Second Military Medical University, Shanghai, China. Since 2015, Dr. Hu leads a research laboratory in the Department of Biophysics, at second military medical university with a faculty position. His laboratory is interested in cancer therapeutics and antibody engineering, primarily development of novel sensitizers for antibody-based therapies (e.g., Anti-ERBB antibodies). Dr. Hu’s research is currently supported by the National Natural Science Foundation of China and Military Medicine Special grant of Second Military Medical University.

Affiliations and Expertise

Lead, Research Laboratory, Department of Biophysics, Second Military Medical University, Shanghai, China

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