Plant-derived Anticancer Drugs

Vipendra Kumar Singh, PhD is a senior postdoctoral fellow in the School of Biosciences and Bioengineering at the Indian Institute of Technology Mandi, Himachal Pradesh, India. Ankit Kumar Singh, PhD works as an Assistant Professor at the University Department of Botany Lalit Narayan Mithila University, Darbhanga, Bihar, India. Neha Garg, PhD is an Assistant Professor at the Institute of Medical Sciences, Department of Medicinal Chemistry, Banaras Hindu University in India.

• List of Contributors xviiPreface xxi1 Utilization of Synthetic Drugs in Cancer: Preclinical and Clinical-based Evidence 1Sandeep Vaidya, Avadh Biharee, Arpita Yadav, Arun Kumar Sharma, Akhlesh Kumar Jain, Suresh Thareja, and Mayank Kumar Singh1.1 Introduction 11.1.1 Cancer Biology and Pathophysiology 21.1.2 Nanomedicine in Cancer Treatments 31.1.2.1 Applications of Nanomedicine in Cancer Treatment 51.1.3 Evolution of Synthetic Anticancer Drugs from Ancient Beliefs to Modern Medicine 61.2 Synthetic Pharmaceutical Anticancer Drugs 81.3 Challenges Faced in Early Drug Development 171.4 Conclusion 20Acknowledgments 21References 212 United States and European Union Regulations: Approved Treatment Modalities for Managing Cancer 29Avadh Biharee, Khushi Gupta, Arpita Yadav, Shivam Kumar kori, Sudha Bhartiya, Kashif sheikh, Sandeep Vaidya, Sushil K. Kashaw, Suresh Thareja, and Mayank Kumar Singh2.1 Introduction 292.2 FDA Strategies for Drug Approval in the United States 312.2.1 Expedited Approval of Anticancer Drugs in the United States 322.3 EMA Approach for Drug Approval in the EU 352.3.1 Expedited Anticancer Drug Approval in EU 362.4 Approved Treatment Modalities for Cancer Care 382.4.1 Conventional Cancer Therapy 392.4.2 Innovative Cancer Treatments 402.4.3 Physical Therapy for Cancer Treatment 412.4.4 Personalized and Precision Medicine 422.5 Quality Control in Cancer Treatment 432.6 Regulatory Frameworks Involved in Drug Approval Process 442.6.1 FDA and EMA Approach to Drug Approval for Cancer Treatment 452.6.1.1 Drug Approval in the United States 462.6.1.2 Drug Approval in the EU 462.6.2 Key Differences in the FDA and the EU Drug Approval Processes 482.6.3 Comparison of the United States and the EU Device Approval 502.7 Challenges Associated in Drug and Devices Regulation and Approval 522.8 Conclusion 53Acknowledgments 54References 543 Survival Rate and Associated Side Effects of Synthetic Drugs in Cancer Patients: A Shred of Clinical Evidence 63Arpita Yadav, Arun Kumar Sharma, Kishan Kumar Pandey, Anu Chaudhary, Avadh Biharee, Sandeep Vaidya, Suresh Thareja, and Mayank Kumar Singh3.1 Introduction 633.2 Synthetic Drugs in Cancer Treatment 653.3 The Evolution of Chemotherapeutic Agents from Alkylators to Modern Drugs 663.4 Cancer Survival Rates: Challenges and Emerging Trends in Treatment and Diagnosis 683.4.1 Targeted Therapies and Immunotherapies: The New Cancer Treatments 693.4.2 Factors Affecting Survival Rates 703.5 Deleterious Effects of Chemotherapeutic Agents and Their Management Strategies 723.6 Side Effects of Synthetic Drugs 743.6.1 Short-term Side Effects 743.6.2 Long-term Side Effects 753.7 Clinical Evidence of Side Effects 763.8 Resistance and Recurrence 763.9 Future Directions of Synthetic Drugs Against Various Types of Cancer 773.10 Conclusion 78Acknowledgments 79References 794 Global Perspectives on Plant-derived Cancer Therapies 91Sayanta Sarkar and Poorwa Awasthi4.1 Introduction 914.2 Phytochemicals in Cancer Therapies 924.2.1 Rosmarinus officinalis L. 934.2.2 Withania somnifera 954.2.3 Hedychium coronarium 974.2.4 Catharanthus roseus 994.2.5 Ocimum sanctum 1004.2.6 Piper betle 1024.3 Phytochemicals in Drug-resistant Cancers 1034.4 Plant-based Nanomedicines in Cancer Therapies 1034.5 Conclusion and Future Perspectives 104References 1065 Integrative Approaches: Combining Conventional and Plant-derived Cancer Therapies 119Poorwa Awasthi, Shweta Goyal, and Sayanta Sarkar5.1 Introduction 1195.2 Conventional Cancer Therapies: Achievements and Limitations 1205.3 Plant-derived Compounds in Cancer Therapy 1245.3.1 Bioactive Molecules and Their Mechanisms 1245.3.1.1 Polyphenols 1245.3.1.2 Alkaloids 1245.3.1.3 Terpenoids 1255.4 Advantages of Natural Products 1255.5 Synergistic Potential of Combination Therapies 1285.5.1 Mechanisms of Synergy 1285.5.2 Common Examples of Cancer with Combination Therapies 1285.5.2.1 Breast Cancer 1295.5.2.2 Lung Cancer 1305.5.2.3 Colorectal Cancer 1315.5.2.4 Prostate Cancer 1325.5.2.5 Ovarian Cancer 1335.5.2.6 Leukemia 1355.5.2.7 Liver Cancer 1365.5.2.8 Brain Cancer 1385.6 Challenges and Future Perspectives 1405.7 Conclusion 142References 1436 Phytochemical Drugs in Cancer: Therapeutic Interventions and Opportunities 159Archana Kumari, Shankar Suman, and Shivam Priya6.1 Introduction 1596.2 Plant-derived Compounds in Cancer Therapy 1606.2.1 Alkaloids and Their Anticancer Effects 1616.2.2 Terpenoids as Potent Anticancer Agents 1616.2.3 Flavonoids: Multifunctional Cancer Fighters 1616.3 Mechanisms of Action of Plant-derived Compounds 1626.3.1 Induction of Apoptosis 1626.3.2 Targeting CSCs 1626.3.3 Antiangiogenic Properties 1636.3.4 Inhibition of Metastasis and Tumor Progression 1636.4 Nanotechnology in Enhancing Plant-derived Compounds 1646.4.1 Improving Bioavailability and Stability Through Nanoparticle Encapsulation 1646.4.2 Targeted Delivery and Reduced Side Effects of Plant-derived Compounds 1646.4.3 Overcoming Multidrug Resistance with Nanotechnology 1646.5 Clinical Trials and Research on Plant-derived Anticancer Compounds 1656.5.1 Clinical Trials of Curcumin in Cancer Therapy 1656.5.2 Paclitaxel and Semisynthetic Taxanes 1656.5.3 Flavonoids in Clinical Studies 1666.6 Challenges and Future Directions in Plant-derived Cancer Therapies 1666.6.1 Issues with Bioavailability and Solubility 1666.6.2 Standardization and Quality Control 1666.6.3 Clinical Validation and Regulatory Challenges 1666.6.4 Potential of Bioinformatics in Drug Discovery 1676.7 Advanced Applications of Bioinformatics in Plant-based Drug Discovery 1686.7.1 Molecular Docking Studies and Predictive Modeling 1686.7.2 Network Pharmacology Approaches 1686.7.3 Genomics and Metabolomics in Identifying Novel Compounds 1696.8 Case Studies of Successful Plant-derived Cancer Therapies 1696.8.1 Green Tea Extracts in Clinical Applications 1696.8.2 Vinca Alkaloids in Clinical Applications 1696.8.3 Resveratrol’s Potential in Cancer Therapy 1706.9 Future Perspectives and Integration into Clinical Oncology 1716.9.1 Development of Combination Therapies 1716.9.2 Role of Personalized Medicine 1716.9.3 Advanced Drug Delivery Systems 1716.10 Conclusion and Future Directions 172References 1747 Plant-derived Anticancer Molecules as Novel Outlook in the Management of Cancers: An In silico and Pharmacophore-based Approaches 183Surya Venkateswara Prabhu Ratnam Kesanapalli, Babli K. Jha, and Laxmi Devi7.1 Introduction 1837.2 Historical Perspective 1847.3 Key Discoveries of Plant-derived Anticancer Compounds 1847.4 Phytochemicals with Anticancer Properties 1857.4.1 Alkaloids 1857.4.2 Flavonoids 1867.4.3 Terpenes 1877.4.3.1 Paclitaxel (Taxol) 1877.4.3.2 Limonene 1877.4.3.3 Phenolics 1877.4.3.4 Polyphenols 1877.4.3.5 Saponins 1887.4.3.6 Lignans 1887.5 Computational Approaches in Phytochemical Research 1887.5.1 In silico Docking Analysis 1897.5.2 Virtual Screening 1907.5.3 Quantitative Structure-Activity Relationship 1907.5.4 Structure-based Screening Method 1917.5.5 Molecular Dynamics Simulations 1927.5.6 Cheminformatics 1927.5.7 Pharmacophore Modeling 1927.5.8 ml and AI in Drug Discovery 1937.6 Novel Therapeutic Approaches 1937.6.1 Phytochemical-based Drug Formulations 1937.6.2 Immunotherapy 1947.6.3 Targeted Therapy 1947.6.4 Nano Catalysts 1947.6.5 Combination Therapies 1947.6.6 Personalized Medicine 1957.6.7 Advanced Drug Delivery Systems 1957.7 Challenges and Future Directions 1967.8 Bioavailability Issues 1967.9 Regulatory Hurdles 1967.9.1 Ethical Considerations and Sustainable Sourcing 1977.10 Advancements in Computational Power and Algorithms 1977.10.1 Quantum Computing 1977.10.2 Explainable AI 1987.10.3 Precision Oncology 1997.10.4 Biomarker Discovery 1997.11 Conclusion 200Acknowledgment 201References 2028 Plant-derived Molecules and Herbal Formulation for Cancer Treatment: in vitro and in vivo Evidence 209Surya Venkateswara Prabhu Ratnam Kesanapalli, Babli K. Jha, and Laxmi Devi8.1 Introduction 2098.2 Historical Use of Herbal Remedies in Cancer 2108.3 Natural Compounds with Anticancer Properties 2118.3.1 Alkaloids 2128.3.2 Flavonoids 2148.3.3 Terpenoids 2148.3.4 Polyphenols 2158.3.5 Saponins 2158.3.6 Lignans 2158.4 Mechanism of Action 2158.5 Natural Remedies in Cancer Treatment 2168.6 Phototherapeutic Approaches in Oncology Care 2188.7 Methodological Approaches 2208.7.1 In silico Studies (Computational Approaches) 2208.7.2 Network Pharmacology 2218.7.3 In vitro Studies (Cell-based Assays) 2218.7.3.1 Cytotoxicity Assays (MTT, Trypan Blue, LDH Assay) 2218.7.3.2 Lactate Dehydrogenase Release Assay 2218.7.4 Apoptosis and Cell Cycle Analysis 2218.7.5 Caspase Activation Assays 2218.7.6 Proliferation and Migration Assays 2218.7.6.1 Bromodeoxyuridine or 5-Ethynyl-2’-deoxyuridine Incorporation Assays 2218.7.6.2 Scratch Wound Healing Assay 2228.7.7 Caco-2 Permeability Assay 2228.7.8 Western Blot and Reverse Transcription-Polymerase Chain Reaction 2228.7.9 Wound Healing and Transwell Migration Assays 2228.8 In vivo Studies (Animal Models) 2228.8.1 Xenograft Models 2228.8.2 Genetically Engineered Mouse Models 2228.8.3 Toxicity and Pharmacokinetics Studies 2228.8.4 Xenograft Tumor Models 2228.8.5 GEMMs in Drug Resistance Studies 2238.8.6 Patient-derived Xenograft Models 2238.9 Ex Vivo and 3D Models 2248.9.1 Patient-derived Organoids 2248.9.2 3D Spheroid Cultures 2248.10 Clinical Trials and Translational Research 2248.10.1 Phases I–III Clinical Trials 2248.10.2 Combination Therapy Studies 2248.11 Nanotechnology-based Delivery Systems 2248.12 Experimental Validation of Computational Predictions 2248.12.1 Machine Learning and Artificial Intelligence in Drug Discovery 2258.12.2 Biophysical and Biochemical Binding Assays 2258.12.3 Advanced Experimental Approaches 2268.12.4 Immunomodulatory Approaches 2268.12.5 Pharmacophore-based Approaches 2268.12.5.1 Targeting Specific Interactions 2268.12.5.2 Guiding Virtual Screening 2278.12.5.3 Enhancing Lead Optimization 2278.12.5.4 Reducing False Positives/Negatives 2278.13 Key Findings 2288.14 Challenges and Future Directions 2288.14.1 Challenges in Standardization and Bioavailability 2288.14.2 Natural Compounds for Supportive Cancer Care 2288.15 Future Studies and Clinical Trials 2298.16 Conclusion 229Acknowledgment 229References 2309 Globalization of Plant-derived Molecules Against Progression and Metastasis of Cancer in the Last Few Decades 239Kavita, Praveen Kumar, Shikha Singh, and Neha Garg9.1 Introduction 2399.2 Plant-derived Molecules in Cancer 2409.2.1 Alkaloids 2409.2.1.1 Camptothecin 2409.2.1.2 Berberine 2519.2.1.3 Evodiamine 2519.2.1.4 Sanguinarine 2529.2.1.5 Matrine 2529.2.1.6 Piperine 2539.2.1.7 Vinblastine and Vincristine 2539.2.1.8 Tetrandrine 2539.2.2 Polyphenols 2549.2.2.1 Flavonoids 2549.2.2.2 Phenolic Acids 2599.2.2.3 Stilbenes 2599.2.2.4 Lignans 2609.2.3 Taxanes and Epipodophyllotoxins 2619.2.3.1 Paclitaxel 2619.2.3.2 Docetaxel 2619.2.4 Glycosides 2629.2.4.1 Rutin 2629.2.4.2 Verbascoside 2629.2.4.3 Russelioside 2629.3 Conclusion and Future Perspectives 263List of Abbreviations 263Conflict of Interest 263Acknowledgment 264References 26410 Quantum Dots for Targeted Delivery of Plant-derived Anticancer Biomolecules 279Rashmi P. Sharma10.1 Introduction 27910.2 Quantum Dots: A Promising Nanomaterial 28310.2.1 Types of QDs 28310.2.1.1 Core-type QDs 28410.2.1.2 Core-shell QDs 28410.2.1.3 Alloyed QDs 28410.2.2 Advantageous Properties of QDs for Targeted Drug Delivery 28510.3 Cellular Delivery of Cancer-targeting QDs 28610.4 Recent Developments in Using QD-based Targeted Drug Delivery 28810.4.1 Taxanes 29010.4.2 Alkaloids 29110.4.3 Polyphenols 29310.4.4 Flavonoids 29510.4.5 Other Plant-derived Anticancerous Compounds 29610.5 Challenges and Future Perspectives 29710.6 Conclusions 299References 29911 Future of Artificial Intelligence and Plant-derived Molecules in Cancer Therapy 313Jyotika Rajawat, Shreya Prakash, and Poorwa Awasthi11.1 Introduction 31311.2 Plant-derived Molecules in Cancer Therapy 31511.2.1 Camptothecin 31511.2.2 Taxol 31611.2.3 Anthocyanins 31611.2.4 Phytosphingosine 31711.2.5 Genistein 31711.3 Natural Plant Extracts with Potential as Anticancer Agents 31911.3.1 Fagonia indica 32011.3.2 Aristolochia baetica 32011.3.3 Catharanthus roseus 32111.3.4 Curcuma longa 32211.3.5 Artemisia annua 32211.4 AI in Cancer Diagnosis and Treatment 32311.5 Role of AI in Advancing Plant-derived Molecules for Cancer Therapy 32711.5.1 High-throughput Screening of Phytochemicals 32711.5.2 Toxicity Prediction and ADMET Profiling 32811.5.3 Target Identification and Validation 33011.5.4 Optimization of Drug Design 33111.5.5 Drug Repurposing 33211.6 Future Perspectives 332References 33312 Scientific Basis of Plant-derived Quantum Dots for Enhancing the Therapeutic Efficacy in Cancer 341Lucky Kumari, Shashi Kumar, Chandramani Batsh, Shachi Mishra, and Akanksha Upadhyay12.1 Introduction 34112.2 Classification of QDs 34412.3 Synthesis of Plant-derived QDs 34612.3.1 Hydrothermal Method 34712.3.2 Microwave Method 34812.3.3 Chemical Oxidation Method 34812.3.4 Pyrolysis Method 34912.4 Plant-derived QDs in Cancer Diagnosis and Therapy 35212.4.1 In vitro Cytotoxicity 35212.4.2 In vivo Cytotoxicity 35312.5 Therapeutic Efficacy 35412.5.1 Photo-induced Cancer Treatment 35512.5.2 Gene Therapy 35612.5.3 Immunotherapy 35712.6 Conclusion and Future Perspectives 359References 36013 Clinical Trials of Plant-derived Molecules and Herbal Formulations for the Treatment of Cancers 367Ankur Kumar13.1 Introduction 36713.2 Clinical Trials of Curcumin 36813.3 Clinical Trials of Catechin and Tea 37313.4 Clinical Trials of Quercetin 37913.5 Clinical Trials of Ginseng Extract 38013.6 Clinical Trials of Genistein 38113.7 Clinical Trial of Resveratrol 38213.8 Clinical Trials of Sulforaphane 38313.9 Clinical Trials of Berberine 38413.10 Clinical Trials of Lycopene 38513.11 Clinical Trials of Chinese Herbal Formulation 38613.12 Clinical Trials of Other Herbal Formulation 39313.13 Clinical Trials of Rutin 39513.14 Clinical Trials of Betulinic Acid 395Competing Interest 396References 39614 Preclinical and Clinical Trials of Plant-derived Nanoparticles in Different Cancers 401Vivek Kumar Pandey and Shailja Tripathi14.1 Introduction 40114.2 Synthesis of Plant-derived Nanoparticles 40214.2.1 Advantages of Plant-derived Nanoparticles 40414.3 PDNPs in Cancers 40514.3.1 Plant-derived Nanoparticles in Cancer Treatment 40614.3.2 Advantages of Plant-derived Nanoparticles in Cancer Treatment 40914.3.3 PDNPs’ Mechanisms of Action in Cancer Therapy 40914.3.4 Plant-derived Nanoparticles in Cancer Therapy 41014.3.5 PDNPs in Clinical Trials for Cancer Treatment 41114.4 PDNPs in Other Metabolic Diseases 41114.5 Challenges and Future Directions 413References 414Index 427