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.
1. Novel Sensitizing Agents for Therapeutic Anti-EGFR Antibodies - p. Page i 2. Cover - p. Page i 3. Front Matter - p. Page ii 4. Table of Contents - p. Page iii 5. Copyright - p. Page iv 6. Cover Image Insert - p. Page v 7. Aims and Scope of Series “Breaking Tolerance to Antibody-Mediated Immunotherapy” - p. Page vi 8. About the Series Editor - p. Page vi 9. Aims and Scope of Volume - p. Page viii 10. About the Volume Editor - p. Page ix 11. Preface - p. Page ix 12. Contributors - p. Page xi 13. List of Illustrations - p. Page xiii 14. List of Tables - p. Page xiv 15. Chapter 1 : Current status of anti-EGFR agents - p. Page xiv 16. Chapter 2 : Molecular mechanisms of resistance to the EGFR monoclonal antibody cetuximab - p. Page 10 17. Chapter 3 : MM-151 overcomes acquired resistance to cetuximab and panitumumab in colorectal cancers harboring EGFR extracellular domain mutations - p. Page 22 18. Chapter 4 : Sym004 anti-EGFR antibody mixture overcomes resistance to anti-EGFR antibodies in metastatic colorectal cancer - p. Page 33 19. Chapter 5 : Broad RTK-targeted therapy overcomes molecular heterogeneity-driven resistance to cetuximab via vectored immunoprophylaxis in colorectal cancer - p. Page 38 20. Chapter 6 : Pan-HER, an antibody mixture, simultaneously targeting EGFR, HER2, and HER3 effectively overcomes resistance to anti-EGFR antibodies - p. Page 45 21. Chapter 7 : Four-in-one antibodies have superior cancer inhibitory activity against EGFR, HER2, HER3, and VEGF through disruption of HER/MET crosstalk - p. Page 52 22. Chapter 8 : Overcoming acquired resistance to cetuximab by combining EGFR- and HER3-neutralizing monoclonal antibodies - p. Page 60 23. Chapter 9 : Dual targeting of EGFR and HER3 with MEHD7945A overcomes acquired resistance to EGFR inhibitors and radiation - p. Page 66 24. Chapter 10 : Targeting ERBB2 overcomes resistance to the anti-EGFR therapeutic antibody cetuximab - p. Page 73 25. Chapter 11 : CT16: A dual antibody targeting both EGFR and Notch suppresses EGFR blockage and radiation resistance by decreasing tumor-initiating cell frequency - p. Page 80 26. Chapter 12 : BET inhibition overcomes receptor tyrosine kinase-mediated cetuximab resistance in HNSCC - p. Page 86 27. Chapter 13 : Dual inhibition of EGFR and c-Src by cetuximab and dasatinib combined with FOLFOX chemotherapy in patients with metastatic colorectal cancer - p. Page 96 28. Chapter 14 : A novel bispecific antibody targeting EGFR and cMet is effective against EGFR inhibitor-resistant lung tumors - p. Page 102 29. Chapter 15 : Use of MET kinase inhibitors to overcome cetuximab resistance in colorectal cancer - p. Page 110 30. Chapter 16 : EGFR- and VEGF(R)-targeted small molecules show synergistic activity in colorectal cancer models refractory to combinations of monoclonal antibodies - p. Page 110 31. Chapter 17 : Antitumor activity of the VEGFR inhibitor ZD6474 in human cancer cells resistant to anti-EGFR therapy - p. Page 121 32. Chapter 18 : Antibody-mediated delivery of anti-KRAS-siRNA overcomes therapy resistance in colon cancer - p. Page 129 33. Chapter 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 - p. Page 133 34. Chapter 20 : MEK1/2 inhibitors AS703026 and AZD6244 may be potential therapies for KRAS-mutated colorectal cancer that is resistant to EGFR monoclonal antibody therapy - p. Page 142 35. Chapter 21 : EGFR/JIP-4/JNK2 signaling attenuates cetuximab-mediated radiosensitization of squamous cell carcinoma cells - p. Page 148 36. Chapter 22 : EGFR/Notch antagonists enhance the response to inhibitors of the PI3K-Akt pathway by decreasing tumor-initiating cell frequency - p. Page 148 37. Chapter 23 : Inhibition of SLC1A5 sensitizes colorectal cancer to cetuximab - p. Page 159 38. Chapter 24 : Targeting of PYK2 synergizes with EGFR antagonists in basal-like TNBC and circumvents HER3-associated resistance via the NEDD4–NDRG1 axis - p. Page 164 39. Chapter 25 : Overcoming acquired resistance to EGFR-targeted therapy by regulating autophagy - p. Page 171 40. Chapter 26 : Hedgehog signaling alters reliance on EGF receptor signaling and mediates anti-EGFR therapeutic resistance in head and neck cancer - p. Page 176 41. Chapter 27 : Novel Toll-like receptor 9 agonist induces epidermal growth factor receptor (EGFR) inhibition and synergistic antitumor activity with EGFR inhibitors - p. Page 182 42. Chapter 28 : Targeted cancer therapy: The future of drug combinations - p. Page 188 43. Index - p. Page 212
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.
1. Novel Sensitizing Agents for Therapeutic Anti-EGFR Antibodies - p. Page i 2. Cover - p. Page i 3. Front Matter - p. Page ii 4. Table of Contents - p. Page iii 5. Copyright - p. Page iv 6. Cover Image Insert - p. Page v 7. Aims and Scope of Series “Breaking Tolerance to Antibody-Mediated Immunotherapy” - p. Page vi 8. About the Series Editor - p. Page vi 9. Aims and Scope of Volume - p. Page viii 10. About the Volume Editor - p. Page ix 11. Preface - p. Page ix 12. Contributors - p. Page xi 13. List of Illustrations - p. Page xiii 14. List of Tables - p. Page xiv 15. Chapter 1 : Current status of anti-EGFR agents - p. Page xiv 16. Chapter 2 : Molecular mechanisms of resistance to the EGFR monoclonal antibody cetuximab - p. Page 10 17. Chapter 3 : MM-151 overcomes acquired resistance to cetuximab and panitumumab in colorectal cancers harboring EGFR extracellular domain mutations - p. Page 22 18. Chapter 4 : Sym004 anti-EGFR antibody mixture overcomes resistance to anti-EGFR antibodies in metastatic colorectal cancer - p. Page 33 19. Chapter 5 : Broad RTK-targeted therapy overcomes molecular heterogeneity-driven resistance to cetuximab via vectored immunoprophylaxis in colorectal cancer - p. Page 38 20. Chapter 6 : Pan-HER, an antibody mixture, simultaneously targeting EGFR, HER2, and HER3 effectively overcomes resistance to anti-EGFR antibodies - p. Page 45 21. Chapter 7 : Four-in-one antibodies have superior cancer inhibitory activity against EGFR, HER2, HER3, and VEGF through disruption of HER/MET crosstalk - p. Page 52 22. Chapter 8 : Overcoming acquired resistance to cetuximab by combining EGFR- and HER3-neutralizing monoclonal antibodies - p. Page 60 23. Chapter 9 : Dual targeting of EGFR and HER3 with MEHD7945A overcomes acquired resistance to EGFR inhibitors and radiation - p. Page 66 24. Chapter 10 : Targeting ERBB2 overcomes resistance to the anti-EGFR therapeutic antibody cetuximab - p. Page 73 25. Chapter 11 : CT16: A dual antibody targeting both EGFR and Notch suppresses EGFR blockage and radiation resistance by decreasing tumor-initiating cell frequency - p. Page 80 26. Chapter 12 : BET inhibition overcomes receptor tyrosine kinase-mediated cetuximab resistance in HNSCC - p. Page 86 27. Chapter 13 : Dual inhibition of EGFR and c-Src by cetuximab and dasatinib combined with FOLFOX chemotherapy in patients with metastatic colorectal cancer - p. Page 96 28. Chapter 14 : A novel bispecific antibody targeting EGFR and cMet is effective against EGFR inhibitor-resistant lung tumors - p. Page 102 29. Chapter 15 : Use of MET kinase inhibitors to overcome cetuximab resistance in colorectal cancer - p. Page 110 30. Chapter 16 : EGFR- and VEGF(R)-targeted small molecules show synergistic activity in colorectal cancer models refractory to combinations of monoclonal antibodies - p. Page 110 31. Chapter 17 : Antitumor activity of the VEGFR inhibitor ZD6474 in human cancer cells resistant to anti-EGFR therapy - p. Page 121 32. Chapter 18 : Antibody-mediated delivery of anti-KRAS-siRNA overcomes therapy resistance in colon cancer - p. Page 129 33. Chapter 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 - p. Page 133 34. Chapter 20 : MEK1/2 inhibitors AS703026 and AZD6244 may be potential therapies for KRAS-mutated colorectal cancer that is resistant to EGFR monoclonal antibody therapy - p. Page 142 35. Chapter 21 : EGFR/JIP-4/JNK2 signaling attenuates cetuximab-mediated radiosensitization of squamous cell carcinoma cells - p. Page 148 36. Chapter 22 : EGFR/Notch antagonists enhance the response to inhibitors of the PI3K-Akt pathway by decreasing tumor-initiating cell frequency - p. Page 148 37. Chapter 23 : Inhibition of SLC1A5 sensitizes colorectal cancer to cetuximab - p. Page 159 38. Chapter 24 : Targeting of PYK2 synergizes with EGFR antagonists in basal-like TNBC and circumvents HER3-associated resistance via the NEDD4–NDRG1 axis - p. Page 164 39. Chapter 25 : Overcoming acquired resistance to EGFR-targeted therapy by regulating autophagy - p. Page 171 40. Chapter 26 : Hedgehog signaling alters reliance on EGF receptor signaling and mediates anti-EGFR therapeutic resistance in head and neck cancer - p. Page 176 41. Chapter 27 : Novel Toll-like receptor 9 agonist induces epidermal growth factor receptor (EGFR) inhibition and synergistic antitumor activity with EGFR inhibitors - p. Page 182 42. Chapter 28 : Targeted cancer therapy: The future of drug combinations - p. Page 188 43. Index - p. Page 212
