Cover Image

Novel sensitizing agents for therapeutic anti-EGFR antibodies /

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.

Bibliographic Details
Corporate Author: ScienceDirect (Online service)
Other Authors: Hu, Shi, Ph. D (Editor)
Format: eBook
Language:English
Published: Amsterdam : Academic Press, [2023]
Series:Sensitizing agents for cancer resistant antibody-targeted therapies ; v. 1
Subjects:
Cancer > Immunotherapy.
Drug resistance in cancer cells.
Epidermal growth factor.
Drug Resistance, Neoplasm
Epidermal Growth Factor
Cancer > Immunothérapie.
Cellules cancéreuses > Résistance aux médicaments.
Facteur de croissance épidermique.
Cancer > Immunotherapy
Drug resistance in cancer cells
Epidermal growth factor
Electronic books.
Online Access:Connect to the full text of this electronic book
Table of Contents:
  • Intro
  • Novel Sensitizing Agents for Therapeutic Anti-EGFR Antibodies
  • Copyright
  • Cover Image Insert
  • Aims and Scope of Series ``Breaking Tolerance to Antibody-Mediated Immunotherapy´´
  • About the Series Editor
  • Aims and Scope of Volume
  • About the Volume Editor
  • Preface
  • Contents
  • Contributors
  • Chapter 1: Current status of anti-EGFR agents
  • Introduction
  • Targeting EGFR
  • Novel EGFR targeting strategies
  • Conclusions
  • References
  • Chapter 2: Molecular mechanisms of resistance to the EGFR monoclonal antibody cetuximab
  • Introduction
  • EGFR biology
  • The role of EGFR in human cancer
  • The function of EGFR-targeted antibodies
  • Cetuximab in the clinic
  • Mechanisms of resistance to EGFR-targeted antibodies
  • EGFR mutations
  • EGFR gene copy number as a predictor of response
  • EGFR ligand state
  • KRAS mutations as a predictor of response
  • BRAF mutation as a predictor of response
  • Mechanisms of resistance against EGFR-targeted antibodies
  • Angiogenesis
  • Disorders of EGFR internalization and degradation
  • Oncogenic shift
  • Subcellular localization of EGFR
  • Epithelial cells transform into mesenchymal cells
  • Constitutive activation of EGFR downstream effector molecules
  • Increased expression of HER family growth factors
  • Concluding remarks
  • References
  • Chapter 3: MM-151 overcomes acquired resistance to cetuximab and panitumumab in colorectal cancers harboring EGFR extrace
  • Introduction
  • EGFR ECD mutations do not affect ligand-receptor binding but do affect antibody-receptor binding
  • MM-151 can inhibit the growth of LIM1215 cells overexpressing EGFR ECD mutants
  • MM-151 can inhibit the growth of cetuximab-resistant clones in spontaneous models
  • MM-151 reduced the frequency of EGFR-ECD allele mutations
  • Discussion
  • References
  • Further reading.
  • Chapter 4: Sym004 anti-EGFR antibody mixture overcomes resistance to anti-EGFR antibodies in metastatic colorectal cancer
  • EGFR and CRC
  • SYM004 compared with cetuximab
  • Cell proliferation and induction of apoptosis
  • EGFR-dependent intracellular signaling/MET activation and ERBB2 amplification
  • Tumor xenograft models of human colorectal cancer
  • HER2
  • Final thoughts and future directions
  • References
  • Chapter 5: Broad RTK-targeted therapy overcomes molecular heterogeneity-driven resistance to cetuximab via vectored immun ...
  • Study on the related functional signaling network pathway based on the drug resistance of targeted monoclonal antibodies in CRC
  • Phased therapeutic strategy of antibody transformation in vivo based on VIP background
  • In vivo experiments were conducted to characterize the relationship between pathway crosstalk of key gene effectors and dru ...
  • Cross design and effect presentation of VIP therapeutic drugs and carriers
  • Final summary and assumption
  • References
  • Chapter 6: Pan-HER, an antibody mixture, simultaneously targeting EGFR, HER2, and HER3 effectively overcomes resistance
  • References
  • Chapter 7: Four-in-one antibodies have superior cancer inhibitory activity against EGFR, HER2, HER3, and VEGF through dis ...
  • Introduction
  • Design and characterization of four-in-one antibodies
  • Four-in-one antibodies can effectively inhibit EGFR, HER2, HER3, and VEGFR2
  • The four-in-one antibody has excellent antitumor activity both in vitro and in vivo
  • Only four-in-one antibodies interfere with HER/MET crosstalk
  • MET/HER signaling is critical for resistance to HER-targeted therapy
  • Four-in-one antibodies can overcome resistance to HER therapy
  • Discussion
  • References
  • Chapter 8: Overcoming acquired resistance to cetuximab by combining EGFR- and HER3-neutralizing monoclonal antibodies.
  • EGFR inhibitor tolerance is related to both EGFR and HER3, which MEHD7945A completely targets
  • MEHD7945A inhibits the growth of two tumor cell lines that are resistant to cetuximab
  • MEHD7945A inhibits the growth of human tumor xenografts that are resistant to EGFR inhibitors
  • MEHD7945A inhibits radiation-induced survival and overcomes cross-resistance to radiation
  • mAb33: A neutralizing anti-HER3 antibody that prevents resistance to an EGF kinase inhibitor
  • Combining osimertinib with mAb33 overcomes resistance by upregulating HER3 and inhibiting the release of the soluble extrac ...
  • Combination of mAb33, cetuximab, and osimertinib inhibits growth of human tumor xenografts by simultaneously inhibiting oth ...
  • The drug combination comprising mAb33 delays relapse of a model derived from a patients metastatic lesion
  • Discussion
  • References
  • Chapter 9: Dual targeting of EGFR and HER3 with MEHD7945A overcomes acquired resistance to EGFR inhibitors and radiat
  • HER3 is an essential regulatory target for acquired drug resistance
  • The mechanism of MEHD7945A in overcoming acquired drug resistance through tumor xenografts and cells
  • Study on the mechanism of MEHD7945A in radiation-damaged cells
  • Final thoughts and future directions
  • References
  • Chapter 10: Targeting ERBB2 overcomes resistance to the anti-EGFR therapeutic antibody cetuximab
  • Introduction
  • ERBB2 amplification mediates cetuximab resistance through Erk1/2 signaling
  • Heregulin activates ERBB2 signaling and mediates resistance to cetuximab without ERBB2 amplification
  • 611-CTF, a C-terminal fragment of HER2, is phosphorylated in cetuximab-resistant cells
  • Targeting ERBB2 signaling overcomes resistance to cetuximab: Preclinical studies
  • Dual inhibition of ERBB2 and EGFR in cetuximab-resistant patients: Clinical trials
  • Conclusion
  • References.
  • Chapter 11: CT16: A dual antibody targeting both EGFR and Notch suppresses EGFR blockage and radiation resistance by decrea
  • Introduction
  • Combined use of EGFR inhibitors and irradiation can promote EMT and stem cell-like properties in NSCLC cells
  • Enrichment of the ALDH+ cell population depends on Notch2/3 receptors
  • Dual blockade of EGFR and Notch2/3 inhibits resistance to EGFR inhibitors in vitro
  • Dual blockade of EGFR and Notch2/3 inhibits resistance to EGFR inhibitors in vivo
  • CT16 enhances the radiosensitivity of cancer cells and reduces the ALDH+ cell populations
  • CT16 can reduce the proliferation of tumor cells and shows good antitumor activity
  • Dual blockade of EGFR and Notch2/3 reduces the number of CSCs and delays tumor recurrence after radiotherapy
  • Discussion
  • References
  • Chapter 12: BET inhibition overcomes receptor tyrosine kinase-mediated cetuximab resistance in HNSCC
  • Introduction
  • The HNSCC model of acquired cetuximab resistance relies on surrogate RTK activity
  • Pharmacological inhibition of BET family members overcame cetuximab resistance in vitro
  • Blocking BET can inhibit the expression of RTK in the HNSCC model of cetuximab
  • RTK overexpression mediates resistance to cetuximab and BET inhibition
  • BET blocking prevents the acquisition of cetuximab resistance in the PDX model of HNSCC patients
  • Expression of RTK and BRD4 genes in a clinical cohort of HNSCC
  • Conclusion
  • References
  • Chapter 13: Dual inhibition of EGFR and c-Src by cetuximab and dasatinib combined with FOLFOX chemotherapy in patien
  • Combination synergistic chemotherapy of mCRC treatment
  • Phase IB: Safety and efficacy
  • Phase II: The role of KRAS mutation
  • RAS amplification and KRAS mutation
  • IBD and KRAS-amplified mCRC
  • Discussion and future directions
  • References.
  • Chapter 14: A novel bispecific antibody targeting EGFR and cMet is effective against EGFR inhibitor-resistant lung tumors
  • References
  • Chapter 15: Use of MET kinase inhibitors to overcome cetuximab resistance in colorectal cancer
  • Introduction
  • EGFR and MET are coexpressed in a genotypically diverse panel of cetuximab-sensitive CRC cell lines
  • Combined activation of EGFR and MET enhances CRC cell proliferation by augmenting the activation of AKT and MAPK
  • HGF induces resistance to cetuximab through MET activation
  • HGF rescues CRC cells from cetuximab-induced G1 arrest
  • HGF rescued the apoptosis of DiFi cells induced by cetuximab
  • HGF rescue occurs via MET-dependent activation of AKT and MAPK
  • Discussion
  • References
  • Chapter 16: EGFR- and VEGF(R)-targeted small molecules show synergistic activity in colorectal cancer models refractory t ...
  • An important oncogenic signaling pathway: Intracellular signal transduction
  • Mechanistic differences and activity comparison between TKIs and mAbs
  • Final thoughts and future directions
  • References
  • Chapter 17: Antitumor activity of the VEGFR inhibitor ZD6474 in human cancer cells resistant to anti-EGFR therapy
  • Introduction
  • ZD6474 efficiently inhibited the growth of EGFR-resistant tumors via inhibition of VEGFR
  • The combination of ZD6474 and cetuximab displayed a synergistic antitumor effect against multiple cancer cell lines
  • Discussion
  • References
  • Chapter 18: Antibody-mediated delivery of anti-KRAS-siRNA overcomes therapy resistance in colon cancer
  • Introduction
  • Generation and characterization of KRAS-siRNA-anti-EGFR antibody complexes
  • In vitro validation of KRAS-siRNA-anti-EGFR antibody complexes: KRAS silencing and tumor inhibitory activity
  • In vivo antitumor effect of the cetuximab-KRAS-esiRNA complex
  • Final thoughts and future directions.