Drug and Therapy Development for Triple Negative Breast Cancer

Pravin Kendrekar works as a Scientist Advisor for White Collar Food & Beverages, Pune, India and T&T Pharmaceuticals, Mumbai, India.Vinayak Adimule works at the Angadi Institute of Technology and Management in Belagavi, India.Tara Hurst works in the School of Health Sciences at Birmingham City University in Edgbaston, UK.

• Preface xiiiPart I History of Breast Cancer 11 Early-Stage Diagnosis of Breast Cancer: Amelioration in Approaches 3Nidhi Manhas, Lalita S. Kumar, and Vinayak Adimule1.1 Introduction 31.2 Imaging Techniques 41.2.1 Mammography (MG) 41.2.2 Ultrasonography (US) 71.2.3 Magnetic Resonance Imaging (MRI) 81.3 Microwave Breast Imaging Methods 101.3.1 Microwave Tomography 111.3.2 Radio-Based Microwave Imaging 121.4 Biomarkers and Biosensors for Breast Cancer Detection 141.4.1 Biomarkers 151.4.1.1 Nucleic Acids 151.4.1.2 Proteins 151.4.1.3 Tumor Cells 161.4.2 Biosensors 161.4.2.1 Electrochemical Biosensors 161.4.2.2 Optical Sensors 171.5 Conclusion 19Acknowledgment 20References 202 DNA Replication Stress and Genome Instability in Breast Cancer 35Kirti Sinha, Pau B. Sang, Priyanka Sharma, and Rishi K. Jaiswal2.1 Introduction 352.2 Causes of Replication Stress and Genomic Instability 362.2.1 Replication Dysfunction 362.2.1.1 Low and Untimely Initiation of Replication 362.2.1.2 Replication Fork Maintenance 372.2.1.3 Mitotic Defects 382.2.2 Transcription-Induced Stress 402.2.2.1 Failed Post-Replication Repair 402.2.3 Genomic Aberrations and Instability 402.2.3.1 Site-Specific Hotspots 402.2.3.2 Amplifier Genome 412.2.3.3 Replication in Inappropriate Metabolic Conditions 412.3 Molecular Mechanism of Genomic Instability 422.3.1 Problems Faced During DNA Damage Repair 432.3.2 Transcriptional Stress 442.3.3 CIN: Result of Defective Mitosis 452.4 Aftermath of Replication Stress on Cell and Its Fate 462.4.1 Conservation of Stalled Replication Forks 462.4.2 Chromosome Segregation Defect Check by HR Repair 472.4.3 Aging, Cell Death, and Senescence 472.5 Therapeutic Approach 482.6 Conclusion 50References 513 Recent Advancement of Nanotherapeutics to Treat Breast Cancer 65Devesh U. Kapoor, Rajat Goyal, Rajiv R. Kukkar, and Rupesh K. Gautam3.1 Introduction 653.2 Pathophysiology of Breast Cancer 663.3 Classification of Breast Cancer 663.4 Techniques for Breast Cancer Detection 683.5 Current Breast Cancer Therapies 683.6 Nanotherapeutics for Breast Cancer Treatment and Metastasis 693.6.1 Nanodiamonds (NDs) 693.6.2 Intrinsic Toxicity Reduction 693.6.3 Diminishing Chemoresistance (CR) 703.6.4 Delivery of Combination Therapeutics Through NDs 703.7 Polymer-Based Nanoparticles (PBNPs) 713.8 Inorganic Nanoparticles (IONPs) 723.9 Hydrogels (HGLs) and Microbubbles (MBs) 743.10 Recent Patents of Nanotherapeutics for Breast Cancer Treatment 763.11 Clinical Trials of Nanotherapeutics for Breast Cancer 763.12 Conclusion and Future Perspectives 77References 784 HER Receptor in Breast Cancer 85Guno S. Chakraborthy4.1 Introduction 854.2 Role of HER Receptors in the Human Body 864.3 HER2 Receptor in Breast Cancer Progression 884.4 Conclusion 88References 895 Human Endogenous Retroviruses in Triple-Negative Breast Cancer 93Tara P. Hurst, Timokratis Karamitros, and Gkikas Magiorkinis5.1 Introduction 935.2 HERVs in Breast Cancer and TNBC 955.3 TROJAN lncRNA and TNBC 965.4 HERVs and Breast Cancer Treatments 975.5 Conclusion 975.6 Search Strategy 97References 98Part II Novel Drug Discovery and Development 1036 Development in Drug Repurposing for the Treatment of Acute Leukemia Complicating Metastatic Breast Cancer 105Nilophar M. Shaikh, Vinayak Adimule, and Santosh Nandi6.1 Introduction 1056.1.1 Acute Leukemia’s 1076.1.2 Mitochondrial cAMP–PKA Signaling 1106.1.3 Nuclear Compartment 1106.1.4 Cytosolic Compartment and Plasma Membrane 1106.2 Conclusion 111References 1117 Novel Pharmaceutical Nanomaterials to Advance the Current Breast Cancer Treatment – Current Trends and Future Perspective 117Steven Mufamadi, Mpho Ngoepe, Aidan Battison, and Itumeleng Zosela7.1 Introduction 1177.2 Graphene-Based Nanomaterials for Breast Cancer 1197.3 Light-Based Nanotechnology for Breast Cancer 1207.3.1 Photodynamic Therapeutic Nanomaterials 1207.3.2 Photothermal Therapeutic Nanomaterials 1227.4 Green Synthesis of Gold Nanoparticles for Breast Cancer 1227.5 Nanocarriers for Gene Therapy and Immunotherapy 1247.6 Conclusion and Recommendations 125References 125Part III Advanced Technologies in Breast Cancer Therapy 1318 Artificial Intelligence-Driven Decisions in Breast Cancer Diagnosis 133Amit Gangwal and Rupesh K. Gautam8.1 Introduction 1338.2 Breast Cancer 1358.3 Diagnosis of Breast Cancer 1368.4 Artificial Intelligence 1388.4.1 Artificial Intelligence and Medical Imaging 1408.5 Conclusion 1428.6 Future Challenges 142References 1449 Establishing Nanotechnology-Based Drug Development for Triple- Negative Breast Cancer Treatment 153Ravinder Verma, Shailendra Bhatt, Rohit Dutt, Manish Kumar, Deepak Kaushik, and Rupesh K. Gautam9.1 Introduction 1539.2 Triple-Negative Breast Cancer 1549.2.1 Molecular Mechanisms (Signaling Pathways) Involved in TNBC Therapeutics 1569.2.1.1 Notch Signaling Pathway 1569.2.1.2 Hedgehog Signaling Pathway 1569.2.1.3 Wnt/β-Catenin 1569.2.1.4 Poly(ADP-Ribose) Polymerase (PARP) Inhibitors 1579.2.1.5 EGFR 1579.2.1.6 Mammalian Target of Rapamycin (mTOR) Inhibitors 1579.2.1.7 TGF-β Signaling Pathway 1589.2.1.8 CSPG4 (Chondroitin Sulfate Proteoglycan) Protein Signaling Pathway 1589.2.2 Conventional Therapeutics 1589.2.3 Promising Nanotechnology Innovations for TNBC Therapy 1599.2.3.1 Nanoparticles (NPs) 1609.2.3.2 Nanoconjugates 1629.2.3.3 Quantum Dots (QDs) 1629.2.3.4 Nano-Diamonds (NDs) 1629.2.3.5 Nanocomposites 1639.2.3.6 Nano-Matryoshkas 1639.2.3.7 Polymeric Micelles (PM): A Miracle Ball in Cancer Therapy 1639.2.3.8 Dendrimers 1639.2.3.9 Folded Graphene: Carbon nanotubes (CNTs) 1649.2.3.10 Virus-Like Particles (VLPs) as Novel Nanovesicles 1649.2.3.11 Liposomes 1649.2.4 Vaccines Under the Clinical Trial (CT) for TNBC Treatment 1659.2.4.1 Peptide-Based Vaccines 1669.2.4.2 Viral Vector-Based Vaccines 1669.2.4.3 Gene-Based Vaccines 1669.2.5 USFDA-Approved Clinical Trials 1669.2.6 Current Status of TNBC Treatment 1679.2.7 Recent Patents Based on Nanoformulations for TNBC Treatment 1679.3 Challenges 1689.4 Future Perspectives on TNBC Metastasis Therapy 1689.4.1 NEO Adjuvant Modeling 1699.4.2 Execution of In Vivo Genetic Screening 1699.4.3 Identification of Effective Drugs for TNBC 1699.4.4 Synergistic Effect of Drugs that Almost Eliminate Tumor 1699.5 Conclusion 169References 17010 Etiology and Therapy of Hormone Receptor-Positive Breast Cancer 181Nalini Kurup and Darshana Warekar10.1 Introduction 18110.2 Etiology 18210.2.1 Role of Estrogen Hormone 18210.2.2 Role of Progesterone Hormone 18210.2.3 Estrogen Receptor (ER) 18310.2.4 Progesterone Receptor (PR) 18410.3 Human Epidermal Growth Factor-2 (HER-2) 18410.4 Various Types of Breast Cancer Detected Under Hormone Receptor Breast Cancer 18510.4.1 Estrogen Receptor (ER) Positive 18510.4.2 Progesterone Receptor (PR) Positive 18510.4.3 Hormone Receptor (HR) Negative 18510.5 Detection 18610.6 Therapy 18710.6.1 Selective Estrogen-Receptor Response Modulators (SERMs) 18810.6.2 Aromatase Inhibitors 18810.6.3 Estrogen-Receptor Down Regulators (ERDs) 18810.6.4 Luteinizing Hormone-Releasing Hormone Agents (LHRH) 18910.7 Limitations of Hormone Therapy 19010.7.1 Tamoxifen 19010.7.2 Raloxifene 19010.7.3 Aromatase Inhibitors 19010.7.4 Fulvestrant 19110.8 Triple-Negative Breast Cancer 19110.8.1 Clinical History of Triple-Negative Breast Cancer 19110.8.2 Imaging Characteristics/Features of Triple-Negative Breast Cancer 19110.8.3 Subtypes of TNBC 19210.8.3.1 Basal-Like Subtype: (i) BL1 (ii) BL 2 19210.8.3.2 Claudine Low Subtype 19210.8.3.3 Immunomodulatory Subtype (IM) 19210.8.3.4 Mesenchymal Subtype (M) 19210.8.3.5 Mesenchymal Stem-Like Subtype (MSL) 19210.8.3.6 Luminal Androgen Receptor Subtype (LAR) 19310.8.4 Treatment of Triple-Negative Breast Cancer 19310.8.5 Advance TNBC 19310.8.6 Pharmacogenomics 19410.9 Conclusion 195References 19611 Donor–Acceptor-Based Heterocyclic Compounds as Chemotherapy and Photothermal Agents in Treatment of Breast Cancer Cell 201Vinayak M. Adimule, Sheetal R. Batakurki, Maya M. Pai, and Santosh Nandi11.1 Introduction 20111.2 Causes for Breast Cancer 20211.3 Imaging and Screening of Breast Cancer 20211.4 Photothermal Therapy (PTT) 20311.5 Acceptor–Donor-Based Heterocyclic Compounds 20811.6 Examples of Organic-Based Donor–Acceptor 21011.6.1 Indocyanine 21011.7 Polymers-Based Agents 21111.7.1 Phthalocyanine 21111.8 Conclusion 212References 213Part IV Regulatory, Clinical Aspects and Case Studies 22112 An Insight into Drug Regulatory Affairs and the Procedures 223Shaik A. Begum and Joshna Rani S12.1 Endpoints of Clinical Trials for the Approval of Cancer Drugs and Biologics 22312.2 Statutory and Regulatory Requirements for Effectiveness 22312.2.1 Endpoints Supporting Previous Oncology Approvals 22412.2.2 Endpoints Based on Tumor Assessments 22512.2.3 Clinical Practice Guideline for the Diagnosis, Staging, and Treatment of Patients with Metastatic Breast Cancer 22512.2.4 Cancer Drug and Diagnostic Regulation by the FDA 22612.2.5 Considerations for Clinical Trial Design and Analysis 22712.2.6 Single-Arm Studies 22712.2.7 Randomized Studies Designed to Demonstrate Noninferiority 22712.3 Clinical Trial Design Considerations 22812.4 Clinical Trial Analysis Issues 22812.5 Use of Pathological Complete Response as an Endpoint to Support Accelerated Approval in Neoadjuvant Treatment of High-Risk Early- Stage Breast Cancer 22812.6 Developing Treatments for Premenopausal Women with Breast Cancer 22912.7 Recommendations by FDA 23012.7.1 Access to Experimental Cancer Drugs 23012.7.2 How to Get a Hold of an Experimental Drug 23012.7.3 Access to More Information (Compassionate Use) 23112.8 What is Right to Try? 23112.9 Examples of Drugs Approved for Breast Cancer 232References 23313 A Comprehensive Review of Some Heat-Shock Proteins in the Development and Progression of Human Breast Cancer 237Xolani H. Makhoba and Ofentse J. Pooe13.1 Introduction 23713.1.1 Cancer and Its Economic Burden on Human 23813.2 Structure-Functional Features of HSPs 23913.2.1 Heat-Shock Protein 40 23913.2.2 Heat-Shock Protein 60 23913.2.3 Heat-Shock Protein 70 24013.2.4 Heat-Shock Protein 90 24113.3 Conclusion and Future Perspectives 242Acknowledgments 244References 24414 Nanoparticle-Based Therapeutics for Triple Negative Breast Cancer 249Isidore A. Egebe and Kamalinder K. Singh14.1 Breast Cancer: State of Research and Practice 24914.2 Triple Negative Breast Cancer (TNBC) and Treatment Approaches 25214.3 Nanoparticle Therapeutics for TNBC 25314.3.1 Metallic Nanoparticles 25514.3.1.1 Gold Nanoparticles (AuNPs) 25514.3.1.2 Silver Nanoparticles (AgNPs) 25514.3.2 Dendrimers 25514.3.3 Lipid-Based Nanoparticles (LNPs) 25614.3.3.1 Liposomes 25614.3.3.2 Nanoemulsions (NEs) 25814.3.3.3 Solid Lipid Nanoparticles (SLNs) 25914.3.3.4 Nanostructured Lipid Carriers (NLCs) 25914.3.3.5 Lipid Polymer Hybrid Nanoparticles (LPH-NPs) 26014.3.4 CRISPR Nanoparticles 26114.3.5 Exosomes (Exo) 26114.3.6 Nucleic Acid (NAs)-Based Therapeutics 26214.4 Ligands Used to Enhance Nanoparticle Therapeutics in TNBC 26214.4.1 Antibodies 26214.4.2 Peptides 26214.4.3 Aptamers 26314.4.4 Small Molecules 26314.5 Conclusion 263References 26415 Current Updates in Breast Cancer Drugs 273Nitu 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. Upaganlawar15.1 Introduction 27315.2 Therapeutic Approaches 27415.2.1 Hormonotherapy 27515.2.2 Chemotherapy 27615.3 Targeted Therapy 27615.3.1 Drug Repurposing 27615.3.2 HER2 Inhibitors 27815.3.3 PARP Inhibitors 28015.3.4 Immunotherapy 28015.3.5 Others Novel Targets 28115.3.5.1 Histone Deacetylase (HDAC) Inhibitors 28115.3.5.2 Angiogenesis Inhibitors 28115.4 Conclusion 284Acknowledgment 284References 285Index 295