The first comprehensive and up-to-date compilation of modern diagnostic and treatment methods for triple negative breast cancer
In Drug and Therapy Development for Triple Negative Breast Cancer, a team of distinguished practitioners delivers an in-depth and authoritative discussion of contemporary methods for treating triple negative breast cancer (TNBC). The editors have included material that covers its molecular causes, initial detection, diagnostic tools, treatment procedures, pharmacology, and new and experimental therapies - including nanotherapeutics and photothermal therapies.
As the first comprehensive compilation of modern treatment methods for TNBC, this reference is an unmatched source of information about current and future treatment approaches, including machine learning methods for earlier detection and more accurate diagnosis. Readers will also find: - A thorough introduction to HER receptors in breast cancers - Comprehensive explorations of the etiology and therapy of hormone receptor-positive breast cancer and the early-stage diagnosis of breast cancer - Application of artificial intelligence to breast cancer diagnosis - New insights on the role of DNA replication stress and genome instability in breast cancer
Perfect for medicinal and pharmaceutical chemists, Drug and Therapy Development for Triple Negative Breast Cancer will also benefit oncologists and professionals working in the pharmaceutical industry or in hospital settings.
Table of Contents
Preface xiii
Part I History of Breast Cancer 1
1 Early-Stage Diagnosis of Breast Cancer: Amelioration in Approaches 3
Nidhi Manhas, Lalita S. Kumar, and Vinayak Adimule
1.1 Introduction 3
1.2 Imaging Techniques 4
1.2.1 Mammography (MG) 4
1.2.2 Ultrasonography (US) 7
1.2.3 Magnetic Resonance Imaging (MRI) 8
1.3 Microwave Breast Imaging Methods 10
1.3.1 Microwave Tomography 11
1.3.2 Radio-Based Microwave Imaging 12
1.4 Biomarkers and Biosensors for Breast Cancer Detection 14
1.4.1 Biomarkers 15
1.4.1.1 Nucleic Acids 15
1.4.1.2 Proteins 15
1.4.1.3 Tumor Cells 16
1.4.2 Biosensors 16
1.4.2.1 Electrochemical Biosensors 16
1.4.2.2 Optical Sensors 17
1.5 Conclusion 19
Acknowledgment 20
References 20
2 DNA Replication Stress and Genome Instability in Breast Cancer 35
Kirti Sinha, Pau B. Sang, Priyanka Sharma, and Rishi K. Jaiswal
2.1 Introduction 35
2.2 Causes of Replication Stress and Genomic Instability 36
2.2.1 Replication Dysfunction 36
2.2.1.1 Low and Untimely Initiation of Replication 36
2.2.1.2 Replication Fork Maintenance 37
2.2.1.3 Mitotic Defects 38
2.2.2 Transcription-Induced Stress 40
2.2.2.1 Failed Post-Replication Repair 40
2.2.3 Genomic Aberrations and Instability 40
2.2.3.1 Site-Specific Hotspots 40
2.2.3.2 Amplifier Genome 41
2.2.3.3 Replication in Inappropriate Metabolic Conditions 41
2.3 Molecular Mechanism of Genomic Instability 42
2.3.1 Problems Faced During DNA Damage Repair 43
2.3.2 Transcriptional Stress 44
2.3.3 CIN: Result of Defective Mitosis 45
2.4 Aftermath of Replication Stress on Cell and Its Fate 46
2.4.1 Conservation of Stalled Replication Forks 46
2.4.2 Chromosome Segregation Defect Check by HR Repair 47
2.4.3 Aging, Cell Death, and Senescence 47
2.5 Therapeutic Approach 48
2.6 Conclusion 50
References 51
3 Recent Advancement of Nanotherapeutics to Treat Breast Cancer 65
Devesh U. Kapoor, Rajat Goyal, Rajiv R. Kukkar, and Rupesh K. Gautam
3.1 Introduction 65
3.2 Pathophysiology of Breast Cancer 66
3.3 Classification of Breast Cancer 66
3.4 Techniques for Breast Cancer Detection 68
3.5 Current Breast Cancer Therapies 68
3.6 Nanotherapeutics for Breast Cancer Treatment and Metastasis 69
3.6.1 Nanodiamonds (NDs) 69
3.6.2 Intrinsic Toxicity Reduction 69
3.6.3 Diminishing Chemoresistance (CR) 70
3.6.4 Delivery of Combination Therapeutics Through NDs 70
3.7 Polymer-Based Nanoparticles (PBNPs) 71
3.8 Inorganic Nanoparticles (IONPs) 72
3.9 Hydrogels (HGLs) and Microbubbles (MBs) 74
3.10 Recent Patents of Nanotherapeutics for Breast Cancer Treatment 76
3.11 Clinical Trials of Nanotherapeutics for Breast Cancer 76
3.12 Conclusion and Future Perspectives 77
References 78
4 HER Receptor in Breast Cancer 85
Guno S. Chakraborthy
4.1 Introduction 85
4.2 Role of HER Receptors in the Human Body 86
4.3 HER2 Receptor in Breast Cancer Progression 88
4.4 Conclusion 88
References 89
5 Human Endogenous Retroviruses in Triple-Negative Breast Cancer 93
Tara P. Hurst, Timokratis Karamitros, and Gkikas Magiorkinis
5.1 Introduction 93
5.2 HERVs in Breast Cancer and TNBC 95
5.3 TROJAN lncRNA and TNBC 96
5.4 HERVs and Breast Cancer Treatments 97
5.5 Conclusion 97
5.6 Search Strategy 97
References 98
Part II Novel Drug Discovery and Development 103
6 Development in Drug Repurposing for the Treatment of Acute Leukemia Complicating Metastatic Breast Cancer 105
Nilophar M. Shaikh, Vinayak Adimule, and Santosh Nandi
6.1 Introduction 105
6.1.1 Acute Leukemia’s 107
6.1.2 Mitochondrial cAMP-PKA Signaling 110
6.1.3 Nuclear Compartment 110
6.1.4 Cytosolic Compartment and Plasma Membrane 110
6.2 Conclusion 111
References 111
7 Novel Pharmaceutical Nanomaterials to Advance the Current Breast Cancer Treatment - Current Trends and Future Perspective 117
Steven Mufamadi, Mpho Ngoepe, Aidan Battison, and Itumeleng Zosela
7.1 Introduction 117
7.2 Graphene-Based Nanomaterials for Breast Cancer 119
7.3 Light-Based Nanotechnology for Breast Cancer 120
7.3.1 Photodynamic Therapeutic Nanomaterials 120
7.3.2 Photothermal Therapeutic Nanomaterials 122
7.4 Green Synthesis of Gold Nanoparticles for Breast Cancer 122
7.5 Nanocarriers for Gene Therapy and Immunotherapy 124
7.6 Conclusion and Recommendations 125
References 125
Part III Advanced Technologies in Breast Cancer Therapy 131
8 Artificial Intelligence-Driven Decisions in Breast Cancer Diagnosis 133
Amit Gangwal and Rupesh K. Gautam
8.1 Introduction 133
8.2 Breast Cancer 135
8.3 Diagnosis of Breast Cancer 136
8.4 Artificial Intelligence 138
8.4.1 Artificial Intelligence and Medical Imaging 140
8.5 Conclusion 142
8.6 Future Challenges 142
References 144
9 Establishing Nanotechnology-Based Drug Development for Triple- Negative Breast Cancer Treatment 153
Ravinder Verma, Shailendra Bhatt, Rohit Dutt, Manish Kumar, Deepak Kaushik, and Rupesh K. Gautam
9.1 Introduction 153
9.2 Triple-Negative Breast Cancer 154
9.2.1 Molecular Mechanisms (Signaling Pathways) Involved in TNBC Therapeutics 156
9.2.1.1 Notch Signaling Pathway 156
9.2.1.2 Hedgehog Signaling Pathway 156
9.2.1.3 Wnt/β-Catenin 156
9.2.1.4 Poly(ADP-Ribose) Polymerase (PARP) Inhibitors 157
9.2.1.5 EGFR 157
9.2.1.6 Mammalian Target of Rapamycin (mTOR) Inhibitors 157
9.2.1.7 TGF-β Signaling Pathway 158
9.2.1.8 CSPG4 (Chondroitin Sulfate Proteoglycan) Protein Signaling Pathway 158
9.2.2 Conventional Therapeutics 158
9.2.3 Promising Nanotechnology Innovations for TNBC Therapy 159
9.2.3.1 Nanoparticles (NPs) 160
9.2.3.2 Nanoconjugates 162
9.2.3.3 Quantum Dots (QDs) 162
9.2.3.4 Nano-Diamonds (NDs) 162
9.2.3.5 Nanocomposites 163
9.2.3.6 Nano-Matryoshkas 163
9.2.3.7 Polymeric Micelles (PM): A Miracle Ball in Cancer Therapy 163
9.2.3.8 Dendrimers 163
9.2.3.9 Folded Graphene: Carbon nanotubes (CNTs) 164
9.2.3.10 Virus-Like Particles (VLPs) as Novel Nanovesicles 164
9.2.3.11 Liposomes 164
9.2.4 Vaccines Under the Clinical Trial (CT) for TNBC Treatment 165
9.2.4.1 Peptide-Based Vaccines 166
9.2.4.2 Viral Vector-Based Vaccines 166
9.2.4.3 Gene-Based Vaccines 166
9.2.5 USFDA-Approved Clinical Trials 166
9.2.6 Current Status of TNBC Treatment 167
9.2.7 Recent Patents Based on Nanoformulations for TNBC Treatment 167
9.3 Challenges 168
9.4 Future Perspectives on TNBC Metastasis Therapy 168
9.4.1 NEO Adjuvant Modeling 169
9.4.2 Execution of In Vivo Genetic Screening 169
9.4.3 Identification of Effective Drugs for TNBC 169
9.4.4 Synergistic Effect of Drugs that Almost Eliminate Tumor 169
9.5 Conclusion 169
References 170
10 Etiology and Therapy of Hormone Receptor-Positive Breast Cancer 181
Nalini Kurup and Darshana Warekar
10.1 Introduction 181
10.2 Etiology 182
10.2.1 Role of Estrogen Hormone 182
10.2.2 Role of Progesterone Hormone 182
10.2.3 Estrogen Receptor (ER) 183
10.2.4 Progesterone Receptor (PR) 184
10.3 Human Epidermal Growth Factor-2 (HER-2) 184
10.4 Various Types of Breast Cancer Detected Under Hormone Receptor Breast Cancer 185
10.4.1 Estrogen Receptor (ER) Positive 185
10.4.2 Progesterone Receptor (PR) Positive 185
10.4.3 Hormone Receptor (HR) Negative 185
10.5 Detection 186
10.6 Therapy 187
10.6.1 Selective Estrogen-Receptor Response Modulators (SERMs) 188
10.6.2 Aromatase Inhibitors 188
10.6.3 Estrogen-Receptor Down Regulators (ERDs) 188
10.6.4 Luteinizing Hormone-Releasing Hormone Agents (LHRH) 189
10.7 Limitations of Hormone Therapy 190
10.7.1 Tamoxifen 190
10.7.2 Raloxifene 190
10.7.3 Aromatase Inhibitors 190
10.7.4 Fulvestrant 191
10.8 Triple-Negative Breast Cancer 191
10.8.1 Clinical History of Triple-Negative Breast Cancer 191
10.8.2 Imaging Characteristics/Features of Triple-Negative Breast Cancer 191
10.8.3 Subtypes of TNBC 192
10.8.3.1 Basal-Like Subtype: (i) BL1 (ii) BL 2 192
10.8.3.2 Claudine Low Subtype 192
10.8.3.3 Immunomodulatory Subtype (IM) 192
10.8.3.4 Mesenchymal Subtype (M) 192
10.8.3.5 Mesenchymal Stem-Like Subtype (MSL) 192
10.8.3.6 Luminal Androgen Receptor Subtype (LAR) 193
10.8.4 Treatment of Triple-Negative Breast Cancer 193
10.8.5 Advance TNBC 193
10.8.6 Pharmacogenomics 194
10.9 Conclusion 195
References 196
11 Donor-Acceptor-Based Heterocyclic Compounds as Chemotherapy and Photothermal Agents in Treatment of Breast Cancer Cell 201
Vinayak M. Adimule, Sheetal R. Batakurki, Maya M. Pai, and Santosh Nandi
11.1 Introduction 201
11.2 Causes for Breast Cancer 202
11.3 Imaging and Screening of Breast Cancer 202
11.4 Photothermal Therapy (PTT) 203
11.5 Acceptor-Donor-Based Heterocyclic Compounds 208
11.6 Examples of Organic-Based Donor-Acceptor 210
11.6.1 Indocyanine 210
11.7 Polymers-Based Agents 211
11.7.1 Phthalocyanine 211
11.8 Conclusion 212
References 213
Part IV Regulatory, Clinical Aspects and Case Studies 221
12 An Insight into Drug Regulatory Affairs and the Procedures 223
Shaik A. Begum and Joshna Rani S
12.1 Endpoints of Clinical Trials for the Approval of Cancer Drugs and Biologics 223
12.2 Statutory and Regulatory Requirements for Effectiveness 223
12.2.1 Endpoints Supporting Previous Oncology Approvals 224
12.2.2 Endpoints Based on Tumor Assessments 225
12.2.3 Clinical Practice Guideline for the Diagnosis, Staging, and Treatment of Patients with Metastatic Breast Cancer 225
12.2.4 Cancer Drug and Diagnostic Regulation by the FDA 226
12.2.5 Considerations for Clinical Trial Design and Analysis 227
12.2.6 Single-Arm Studies 227
12.2.7 Randomized Studies Designed to Demonstrate Noninferiority 227
12.3 Clinical Trial Design Considerations 228
12.4 Clinical Trial Analysis Issues 228
12.5 Use of Pathological Complete Response as an Endpoint to Support Accelerated Approval in Neoadjuvant Treatment of High-Risk Early- Stage Breast Cancer 228
12.6 Developing Treatments for Premenopausal Women with Breast Cancer 229
12.7 Recommendations by FDA 230
12.7.1 Access to Experimental Cancer Drugs 230
12.7.2 How to Get a Hold of an Experimental Drug 230
12.7.3 Access to More Information (Compassionate Use) 231
12.8 What is Right to Try? 231
12.9 Examples of Drugs Approved for Breast Cancer 232
References 233
13 A Comprehensive Review of Some Heat-Shock Proteins in the Development and Progression of Human Breast Cancer 237
Xolani H. Makhoba and Ofentse J. Pooe
13.1 Introduction 237
13.1.1 Cancer and Its Economic Burden on Human 238
13.2 Structure-Functional Features of HSPs 239
13.2.1 Heat-Shock Protein 40 239
13.2.2 Heat-Shock Protein 60 239
13.2.3 Heat-Shock Protein 70 240
13.2.4 Heat-Shock Protein 90 241
13.3 Conclusion and Future Perspectives 242
Acknowledgments 244
References 244
14 Nanoparticle-Based Therapeutics for Triple Negative Breast Cancer 249
Isidore A. Egebe and Kamalinder K. Singh
14.1 Breast Cancer: State of Research and Practice 249
14.2 Triple Negative Breast Cancer (TNBC) and Treatment Approaches 252
14.3 Nanoparticle Therapeutics for TNBC 253
14.3.1 Metallic Nanoparticles 255
14.3.1.1 Gold Nanoparticles (AuNPs) 255
14.3.1.2 Silver Nanoparticles (AgNPs) 255
14.3.2 Dendrimers 255
14.3.3 Lipid-Based Nanoparticles (LNPs) 256
14.3.3.1 Liposomes 256
14.3.3.2 Nanoemulsions (NEs) 258
14.3.3.3 Solid Lipid Nanoparticles (SLNs) 259
14.3.3.4 Nanostructured Lipid Carriers (NLCs) 259
14.3.3.5 Lipid Polymer Hybrid Nanoparticles (LPH-NPs) 260
14.3.4 CRISPR Nanoparticles 261
14.3.5 Exosomes (Exo) 261
14.3.6 Nucleic Acid (NAs)-Based Therapeutics 262
14.4 Ligands Used to Enhance Nanoparticle Therapeutics in TNBC 262
14.4.1 Antibodies 262
14.4.2 Peptides 262
14.4.3 Aptamers 263
14.4.4 Small Molecules 263
14.5 Conclusion 263
References 264
15 Current Updates in Breast Cancer Drugs 273
Nitu L. Wankhede, Mayur B. Kale, Pranali A. Chandurkar, Manish M. Aglawe, Ashwini K. Bawankule, Brijesh G. Taksande, Milind J. Umekar, Rupesh K. Gautam, and Aman B. Upaganlawar
15.1 Introduction 273
15.2 Therapeutic Approaches 274
15.2.1 Hormonotherapy 275
15.2.2 Chemotherapy 276
15.3 Targeted Therapy 276
15.3.1 Drug Repurposing 276
15.3.2 HER2 Inhibitors 278
15.3.3 PARP Inhibitors 280
15.3.4 Immunotherapy 280
15.3.5 Others Novel Targets 281
15.3.5.1 Histone Deacetylase (HDAC) Inhibitors 281
15.3.5.2 Angiogenesis Inhibitors 281
15.4 Conclusion 284
Acknowledgment 284
References 285
Index 295
