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MULTI-DRUG RESISTANCE IN CANCER The book details the mechanisms underlying multi-drug cellular resistance and the targets of novel chemotherapeutic agents. Cancer is a major killer all over the world. Even with all the progress made, chemotherapy is still the mainstay of modern cancer treatment. The progression of the cellular defeat of numerous independent anticancer drugs in terms of their chemical structure is a major barrier to successful chemotherapy. Multi-drug resistance (MDR) is a term for the fact that most cancer patients exhibit this phenomenon. According to the numbers, drug…mehr
MULTI-DRUG RESISTANCE IN CANCER The book details the mechanisms underlying multi-drug cellular resistance and the targets of novel chemotherapeutic agents. Cancer is a major killer all over the world. Even with all the progress made, chemotherapy is still the mainstay of modern cancer treatment. The progression of the cellular defeat of numerous independent anticancer drugs in terms of their chemical structure is a major barrier to successful chemotherapy. Multi-drug resistance (MDR) is a term for the fact that most cancer patients exhibit this phenomenon. According to the numbers, drug resistance carries the blame for 90% of cancer patient deaths. Refractory cancer and tumor recurrence are common outcomes of prolonged chemotherapy. Because of the prevalence of drug-resistance mutations, the difficulty of treating tumors increases and the therapeutic efficacy of drugs decreases. Multi-Drug Resistance in Cancer: Mechanism and Treatment Strategies contains nine chapters that cover topics such as: studying the mechanics of resistance to drugs by autophagy; studies to delineate the role of efflux transporters; expression of drug transporters; resistance to targeted therapies in breast cancer; advances in metallodrug driven combination treatment for cancer; and use of natural agents for the overcoming of cancer drug resistance. The book aims to provide the latest data on the mechanisms of cellular resistance to anticancer agents currently used in clinical treatment. It provides a better understanding of the mechanisms of MDR and targets of novel chemotherapy agents which should guide future research concerning new effective strategies in cancer treatment. Audience This book is written for pharmaceutical and biomedical scientists and researchers at both the bench and in the clinic who are interested in the mechanisms and strategies for overcoming cancer's multi-drug resistance.
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Rishabha Malviya, PhD, is an associate professor in the Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University. He has authored more than 150 research/review papers for national/international journals of repute and has been granted more than 10 patents from various countries while a further 40 patents are published/under evaluation. His areas of interest include formulation optimization, nanoformulation, targeted drug delivery, localized drug delivery, and characterization of natural polymers as pharmaceutical excipients. Arun Kumar Singh has completed M. Pharm (pharmaceutics) from Galgotias University, Greater Noida, India. His areas of interest are in the area of nanoformulation, blockchain, IoT, machine learning, cancer, artificial intelligence, and big data. Deepika Yadav completed M. Pharm from Galgotias University, Greater Noida, Uttar Pradesh. She has published several papers with reputed international publishers.
Inhaltsangabe
Foreword xiii
Preface xv
Acknowledgment xvii
1 Multi- Drug Resistance in Cancer: Understanding of Treatment Strategies 1 Rishabha Malviya, Arun Kumar Singh and Deepika Yadav
1.1 Introduction 1
1.2 Both Congenital and Developed Resistance to Drugs 3
1.2.1 Intrinsic Resistance 3
1.2.2 Acquired Resistance 4
1.3 Drug- Resistance Mechanisms 6
1.3.1 Increased Efflux of Drugs 6
1.3.2 Impact on Medication Target 7
1.3.3 Improved DNA- Damage Repair 9
1.4 Senescence Escape 9
1.5 Epigenetic Alterations 9
1.6 Tumor Heterogeneity 10
1.7 Tumor Microenvironment 11
1.8 Epithelial to Mesenchymal Transition 13
1.9 Conclusion 15
References 18
2 Understanding Different Mechanisms Involved in Cancer Drug Resistance: Proposing Novel Strategies to Overcome MDR 31 Rishabha Malviya, Arun Kumar Singh and Deepika Yadav
2.1 Introduction 31
2.2 Drug Resistance: Internal and External Variables 33
2.2.1 Phenotypic Variation of Tumors 33
2.2.2 Tumor Microenvironment 33
2.2.3 Cancer Stem Cells 33
2.2.4 Inactivation of the Anticancer Drugs 34
2.2.5 Multi-Drug Resistance 35
2.2.6 Increasing the Release of Drugs Outside the Cell 35
2.2.7 Reducing the Absorption of the Drugs 36
2.2.8 Inhibition of Cell Death (Apoptosis Pathway Blocking) 36
2.3 Improving the Pharmacokinetics 37
2.4 Changing the Aim of the Chemotherapy Agents 37
2.5 Improving the DNA Repair Process 39
2.5.1 Augmentation of a Gene 39
2.5.2 Epigenetic Altering Caused Drug Resistance 39
2.6 MicroRNA in Cancer Drug Resistance 40
2.7 Conclusion 41
References 41
3 Molecular Mechanism of Multi-Drug Resistant Cancer Cells 47 Rishabha Malviya, Arun Kumar Singh and Deepika Yadav
3.1 Introduction 47
3.2 Types of Drug Resistance 48
3.3 Mechanisms of Drug Resistance 49
3.3.1 Drug Efflux via ABC Transporters 49
3.3.2 Permeability Glycoprotein/MDR- 1 51
3.3.3 Multi-Drug Resistance Protein 52
3.3.4 Breast Cancer Resistance Protein 53
3.4 Reduction in Drug Activity and Cellular Absorption 54
3.5 Instability in the Genome and Medication Resistance 56
3.5.1 Mutation and Medication Target Alteration 56
3.5.2 Restoration of DNA Integrity 57
3.5.3 Resistant Genes and Epigenetic Modifications 58
3.5.4 Drug Resistance and Programmed Cell Death 59
3.6 RNA Interference Therapy 62
3.7 Methods of Physical Intervention to Treat MDR 64
3.8 Conclusion 65
References 66
4 Natural Products for Clinical Management of Drug Resistant Cancer Cells 77 Rishabha Malviya, Arun Kumar Singh and Deepika Yadav
4.1 Introduction 77
4.2 Resistance Mechanisms 78
4.3 Antitumor Plants for Multi-Drug- Resistant Cells 79
4.4 Qualea Species and Their Medical Applications 82
4.5 Antitumor Activity of Qualea Grandiflora and Qualea Multiflora 83
4.6 Conclusion 83
References 84
5 Understanding of Autophagy to Combat MDR During Anticancer Therapy 87 Rishabha Malviya, Arun Kumar Singh and Deepika Yadav
1 Multi- Drug Resistance in Cancer: Understanding of Treatment Strategies 1 Rishabha Malviya, Arun Kumar Singh and Deepika Yadav
1.1 Introduction 1
1.2 Both Congenital and Developed Resistance to Drugs 3
1.2.1 Intrinsic Resistance 3
1.2.2 Acquired Resistance 4
1.3 Drug- Resistance Mechanisms 6
1.3.1 Increased Efflux of Drugs 6
1.3.2 Impact on Medication Target 7
1.3.3 Improved DNA- Damage Repair 9
1.4 Senescence Escape 9
1.5 Epigenetic Alterations 9
1.6 Tumor Heterogeneity 10
1.7 Tumor Microenvironment 11
1.8 Epithelial to Mesenchymal Transition 13
1.9 Conclusion 15
References 18
2 Understanding Different Mechanisms Involved in Cancer Drug Resistance: Proposing Novel Strategies to Overcome MDR 31 Rishabha Malviya, Arun Kumar Singh and Deepika Yadav
2.1 Introduction 31
2.2 Drug Resistance: Internal and External Variables 33
2.2.1 Phenotypic Variation of Tumors 33
2.2.2 Tumor Microenvironment 33
2.2.3 Cancer Stem Cells 33
2.2.4 Inactivation of the Anticancer Drugs 34
2.2.5 Multi-Drug Resistance 35
2.2.6 Increasing the Release of Drugs Outside the Cell 35
2.2.7 Reducing the Absorption of the Drugs 36
2.2.8 Inhibition of Cell Death (Apoptosis Pathway Blocking) 36
2.3 Improving the Pharmacokinetics 37
2.4 Changing the Aim of the Chemotherapy Agents 37
2.5 Improving the DNA Repair Process 39
2.5.1 Augmentation of a Gene 39
2.5.2 Epigenetic Altering Caused Drug Resistance 39
2.6 MicroRNA in Cancer Drug Resistance 40
2.7 Conclusion 41
References 41
3 Molecular Mechanism of Multi-Drug Resistant Cancer Cells 47 Rishabha Malviya, Arun Kumar Singh and Deepika Yadav
3.1 Introduction 47
3.2 Types of Drug Resistance 48
3.3 Mechanisms of Drug Resistance 49
3.3.1 Drug Efflux via ABC Transporters 49
3.3.2 Permeability Glycoprotein/MDR- 1 51
3.3.3 Multi-Drug Resistance Protein 52
3.3.4 Breast Cancer Resistance Protein 53
3.4 Reduction in Drug Activity and Cellular Absorption 54
3.5 Instability in the Genome and Medication Resistance 56
3.5.1 Mutation and Medication Target Alteration 56
3.5.2 Restoration of DNA Integrity 57
3.5.3 Resistant Genes and Epigenetic Modifications 58
3.5.4 Drug Resistance and Programmed Cell Death 59
3.6 RNA Interference Therapy 62
3.7 Methods of Physical Intervention to Treat MDR 64
3.8 Conclusion 65
References 66
4 Natural Products for Clinical Management of Drug Resistant Cancer Cells 77 Rishabha Malviya, Arun Kumar Singh and Deepika Yadav
4.1 Introduction 77
4.2 Resistance Mechanisms 78
4.3 Antitumor Plants for Multi-Drug- Resistant Cells 79
4.4 Qualea Species and Their Medical Applications 82
4.5 Antitumor Activity of Qualea Grandiflora and Qualea Multiflora 83
4.6 Conclusion 83
References 84
5 Understanding of Autophagy to Combat MDR During Anticancer Therapy 87 Rishabha Malviya, Arun Kumar Singh and Deepika Yadav
5.1 Introduction 87
5.2 Mechanisms of Autophagy 89
5.2.1 Phagophore Assembly 89
5.2.2 Autophagosome Formation and Maturation 90
5.2.3 Autolysosome Degradation 90
5.2.4 Core Regulator of Autophagy 90
5.3 Mechanisms of MDR 91
5.4
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