Novel sensitizing agents for therapeutic anti-EGFR antibodies / edited by Shi Hu.

Format:

Book

Contributor:

Hu, Shi, editor.

Series:

Breaking Tolerance to Antibody-Mediated Immunotherapy Series

Breaking Tolerance to Antibody-Mediated Immunotherapy ; v.Volume 1

Language:

English

Subjects (All):

Cancer--Immunotherapy.

Cancer.

Drug resistance in cancer cells.

Epidermal growth factor.

Drug Resistance, Neoplasm.

Epidermal Growth Factor.

Medical Subjects:

Drug Resistance, Neoplasm.

Epidermal Growth Factor.

Physical Description:

1 online resource (258 pages)

Edition:

1st ed.

Place of Publication:

London, England : Academic Press, [2023]

Summary:

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.

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

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

Chapter 3: MM-151 overcomes acquired resistance to cetuximab and panitumumab in colorectal cancers harboring EGFR extrace

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

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

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

Chapter 6: Pan-HER, an antibody mixture, simultaneously targeting EGFR, HER2, and HER3 effectively overcomes resistance

Chapter 7: Four-in-one antibodies have superior cancer inhibitory activity against EGFR, HER2, HER3, and VEGF through dis ...

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

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

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

Chapter 10: Targeting ERBB2 overcomes resistance to the anti-EGFR therapeutic antibody cetuximab

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

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

Chapter 12: BET inhibition overcomes receptor tyrosine kinase-mediated cetuximab resistance in HNSCC

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

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

Chapter 14: A novel bispecific antibody targeting EGFR and cMet is effective against EGFR inhibitor-resistant lung tumors

Chapter 15: Use of MET kinase inhibitors to overcome cetuximab resistance in colorectal cancer

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

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

Chapter 17: Antitumor activity of the VEGFR inhibitor ZD6474 in human cancer cells resistant to anti-EGFR therapy

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

Chapter 18: Antibody-mediated delivery of anti-KRAS-siRNA overcomes therapy resistance in colon cancer

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.

References.

Notes:

Includes bibliographical references and index.

Description based on print version record.

Description based on publisher supplied metadata and other sources.

Other Format:

Print version: Hu, Shi Novel Sensitizing Agents for Therapeutic Anti-EGFR Antibodies

ISBN:

9780128215852

9780128215845

OCLC:

1351198957