Overcoming Cancers Resistant to HER-2 Antibodies / Benjamin Bonavida, editor.

Format:

Book

Contributor:

Bonavida, Benjamin, editor.

Series:

Breaking Tolerance to Antibody-Mediated Immunotherapy Series

Breaking Tolerance to Antibody-Mediated Immunotherapy Series ; Volume 2

Language:

English

Subjects (All):

Breast--Cancer.

Breast.

Physical Description:

1 online resource (232 pages)

Edition:

First edition.

Place of Publication:

Amsterdam : Academic Press, [2024]

Summary:

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.

Contents:

Intro

Overcoming Cancers Resistant to HER-2 Antibodies

Copyright

Cover image insert

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´´

Contents

Contributors

Chapter 1: Resistance of breast cancer brain metastasis to trastuzumab therapy

Introduction

Trastuzumab mechanism of action

Notable mechanisms of HER2+ BCBM resistance to trastuzumab

Metalloproteases

Posttranslational modification of HER2 receptor

Mucins

PTEN deficiency

Aberrant expression of downstream HER2 signaling proteins mediate trastuzumab resistance

Epigenetic alterations via noncoding RNAs

Blood-brain barrier

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

Dual HER2 inhibition

Antibody-drug conjugates

Tyrosine kinase inhibitors in combination with HER2-targeted antibody

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

Treatment options for breast cancer

General features of HER2

General

HER2 signaling, ligands, intracellular signaling pathways, and outcome

HER2 overexpression and mutations

Treatment of HER2-expressing breast cancer

Trastuzumab

General properties

Mechanisms of resistance to trastuzumab treatment

Lack or weak expression of HER2

Alteration of the extracellular domain and binding site of the HER2 proteins.

HER2 homodimerization and resistance to trastuzumab (Fig. 8)

Other mechanisms of resistance to trastuzumab

Trastuzumab-drug conjugates to overcome trastuzumab resistance

T-DMI

T-DXd

Remarks and perspectives

Acknowledgments

Chapter 3: Understanding mechanisms of resistance to HER2-targeted therapies in HER2-positive breast cancer

HER2-targeted therapeutic effector mechanisms

Monoclonal antibodies

Tyrosine kinase inhibitors

Resistance mechanisms to HER2-targeted therapies

Impaired HER2 binding

HER family alterations

Compensatory pathway activation

HER2 expression level and HER2 heterogeneity

Unique ADC resistance mechanism

Conclusions

Chapter 4: Clinical implications and management strategies of resistance to anti-HER2 antibodies in breast cancer

HER2 signaling in MBC and targeted therapy

Tackling HER2-positive MBC with targeted therapies and improved survival

Emerging HER2-targeted therapies for MBC

ADCs as developing HER2-targeted therapy

HER2/HER2 bispecific antibodies as revolutionary therapeutics for HER2-positive MBC

Emerging pathways of anti-HER2 therapy insensitivity and new therapeutic targets

Anti-HER2 therapy resistance with clinical challenge and management strategies

Specific drug resistance targets in HER2+ MBC

Novel therapeutic for HER2-positive MBC in clinical trial

Future prospects

Chapter 5: Overexpression of antiapoptotic gene products and resistance to trastuzumab treatment of breast cancer

Breast cancer resistances to conventional treatments

HER2 overexpression and signaling

PI3K signaling

MAPK signaling

The anti-HER2 mAb trastuzumab

General trastuzumab resistance mechanisms.

Trastuzumab and antiapoptotic proteins

Bcl-2 overexpression in HER2 positive cancers

Bcl-xL overexpression in HER2 positive cancers

Survivin overexpression in HER2 positive cancers

Mcl-1 overexpression in HER2 positive cancers

Targeting antiapoptotic gene products to restore response to trastuzumab

PI3K inhibitors

miRNAs

BH3 mimetics and Mcl-1 inhibitors

Combination of trastuzumab with anticancer immunotherapy

Immune checkpoint inhibitors

Bispecific antibodies

CAR-T cells

Conclusions and future perspectives

Chapter 6: How does understanding epigenetics help circumvent HER-2 antibody resistance?

Molecular target therapy and anti-HER2 antibody mechanism of action and their combinations with other antineoplastic drugs

The ErbB family

Overview of the anti-HER2 antibody mechanism

Mechanism of action by isolated therapies directed to HER2 overexpression

Trastuzumab (Herceptin)

Pertuzumab (Perjeta)

Mechanism of action in combined therapies directed to HER2 overexpression

Inhibition of growth factor receptors

Two monoclonal antibodies (pertuzumab and trastuzumab) blockage

Trastuzumab and TKIs (tyrosine kinase inhibitor) combination

Bivalent anti-HER2 antibodies and similar ones

Anti-HER2 drug-antibody conjugates-First targeted chemotherapy for solid tumors

Inhibition of HER2 pathway downstream signaling in combination with trastuzumab

mTOR inhibitors

Dual mTOR-PI3K inhibitors

AKT inhibitors

Membrane protein inhibitors plus trastuzumab

Histone deacetylase (HDAC) inhibitors in combination with trastuzumab

HSP90 inhibitors in combination with trastuzumab

Insulin-type growth factor I (IGF-1R) inhibitors in combination with trastuzumab.

P130Cas protein inhibition/mTOR inhibition in combination with trastuzumab

TGF-β growth factor inhibitors in combination with trastuzumab

TK EphA2 receptor inhibitors plus trastuzumab

Fatty acid synthase inhibitors

Angiogenesis inhibitors in combination with trastuzumab

Epigenetics and resistance to treatments: Mechanistic detailing

Therapeutic antibodies and main clinical trials

Impact on immune response and cell cycle

Perspectives

Chapter 7: Resistance of HER2-expressing ovarian cancer to trastuzumab and mechanisms of overcoming resistance

HER overview/HER2 expression

Mechanisms of HER2 overexpression in cancer

Mechanisms of HER2 overexpression

Transcriptional regulation

Epigenetics

MicroRNAs

Activation of signaling pathways by HER2 overexpression and associated consequences

EGFR family activation of the PI3K pathway

EGFR family activation of the MAPK pathway

EGFR family activation of the PLCγ/PKC pathway

Trastuzumab treatment of ovarian cancer

Mechanisms of action

HER2 degradation/endocytosis

Antibody-dependent cellular cytotoxicity (ADCC)

Inhibition of HER2 dimerization and impact on the PI3K and MAPK pathways

Cleavage blocking

Efficacy

Mechanisms of resistance

Lack of HER2 expression

HER2 mutations

Epitope masking

Overactivation of the alternative tyrosine kinase receptors

Abnormal activation of the PI3K pathway/loss of PTEN function

Immune response

Tumor microenvironment factors

Hypoxia

Inflammation

Stromal interactions

Overcoming resistance to trastuzumab

Trastuzumab conjugates

Combinations with chemo or targeted therapies

Discussion and future perspectives

References.

Chapter 8: Clinical implications of resistance to anti-HER2 antibodies in breast cancer

Resistance to anti-HER2 monotherapies

Impaired interaction of trastuzumab to HER2

Reduced HER2 expression

Variants of HER2-receptor or molecular masking

Altered intracellular signaling

By constitutive activation of PI3K/AKT-mediated mTOR pathway

HER2 cross-signaling

Expression of estrogen receptors (ER)

Activation of the cyclin D1-cyclin-dependent kinase 4/6 (CDK4/6) pathway

Overexpression of fatty acid synthase (FASN)

Evasion of antibody-dependent cellular cytotoxicity (ADCC)

Lapatinib

HER2 gene mutations

Activation of pathways that run parallel to HER2

Elevated levels of RTK ligands

Changes in signaling via HER2-HER3 heterodimers

Activation of the cyclin D1-CDK4/6 pathway

Stimulation of signaling cascades downstream of HER2

Changes in the PI3K/AKT/mTOR pathway

Alterations in oncogenes and tumor suppressor genes

Trastuzumab-Emtansine drug conjugate

Altered HER2 binding

Activation of signaling pathways

Dual HER2 blockage

Trastuzumab and Lapatinib combination

Altered intracellular signaling pathways

Trastuzumab plus Pertuzumab

Chapter 9: Highlights of current and future for the treatment of resistant HER2+ breast cancer to HER

New therapeutic approaches to overcome resistance

Antibody-drug conjugates (ADCs)

Trastuzumab duocarmycin (SYD985)

ARX788

Distamab vedotin (RC48-ADC)

Zanidatamab (ZW25)

Zenocutuzumab (M+CLA-128)

Targeting protein degraders

Harnessing the immune system

Combination treatments with checkpoint inhibitors (CPIs)

Bispecific engagers

CAR-T/NK/M therapy for HER2-positive MBC.

Cancer vaccines targeting HER2.

Notes:

Includes bibliographical references and index.

Description based on publisher supplied metadata and other sources.

Description based on print version record.

Other Format:

Print version: Bonavida, Benjamin Overcoming Cancers Resistant to HER-2 Antibodies

ISBN:

9780128167380

OCLC:

1450100511