Cancer Epigenetics and Nanomedicine

Dr. Prashant Kesharwani is an assistant professor of pharmaceutics at School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India. He has more than 12 years of teaching, research, and industrial experience at international levels from various countries, including the United States, Malaysia, and India. An overarching goal of his current research is the development of nanoengineered drug delivery systems for various diseases. He has more than 300 international publications in well-reputed journals and more than 25 international books (Elsevier). He is a recipient of many research grants from various funding bodies. He is also the recipient of several internationally acclaimed awards, such as “USERN Laureate award”, most prestigious “Ramanujan Fellowship Award”. He actively participates in outreach and scientific dissemination for the service of the wider community. Dr. Chitra Thakur is an Assistant Professor-Research in the Department of Pathology at the Stony Brook Cancer Center, New York, USA. She is a cancer biologist and has expertise in molecular oncology, mouse models of human cancers, analyzing big data in translational research, toxicology, and epigenetics in human cancers. She is the recipient of several internationally acclaimed awards such as the “DFG German Excellence Initiative Award,”, “NIH-Big Data Training for Translational Omics Research” and “American Cancer Society IRG”. With more than 45 research articles published in mainstream scientific journals, she has contributed significantly towards the understanding of the molecular mechanisms in human cancers. She is engrossed in cancer research, teaching, and community outreach initiatives, hence fostering the scientific community and health care professionals engaged in cancer diagnosis, and treatment.

About the editors
Preface
Acknowledgments

SECTION 1 Overview of cancer, internal and external factors associated with cancer

CHAPTER 1 Overview of cancer: Mechanisms of carcinogenesis
Uttara Saran and Chitra Thakur

Introduction
Cancer: A historical perspective
Origin of cancer: Theories and drivers of carcinogenesis
Theories of cancer origin
Mechanisms of carcinogenesis
Hallmarks of cancer
Epigenetics and cancer
DNA methylation in cancer
Histone modifications
Nucleosome positioning
Noncoding RNAs
Conclusion
References

CHAPTER 2 Tumor metabolism and micronutrients: New insights to target malignant tumors
Santhi Latha Pandrangi, Prasanthi Chittineedi, and Sireesha V. Garimella

Introduction
Role of micronutrients in targeting malignant tumors
Impact of iron levels on cancer proliferation
Targeting intracellular iron levels to induce cellular death
Impact of calcium levels on cancer proliferation
Targeting calcium levels to induce cellular death
Impact of magnesium levels on cancer proliferation
Targeting Warburg effect to induce tumor cell death
Role of glycolytic enzymes in inducing cancer cell death
Other metabolic pathways used by tumor cells
Interplay between glutaminolysis and Warburg effect
Discussion and conclusion
Author contributions
Conflict of interest
Acknowledgments
References

CHAPTER 3 The role of one-carbon amino acids in tumor-immune metabolism: From oncogenesis to therapy
Suchandrima Saha and Monisankar Ghosh

Introduction
One-carbon metabolism
Methionine
Serine
One-carbon metabolism and T-cell function
Dependency of methionine metabolism in T-cells
Dependency of serine metabolism in T-cells
Restriction of AAs as therapy
Therapeutic restriction of methionine
Therapeutic restriction of serine
Conclusion and future directions
References

CHAPTER 4 Environmental causes of cancer
Priya Wadgaonkar

Introduction
Smoking and tobacco use
Radiation
Alcohol consumption
Diet and obesity
Air pollution
Water pollution
Soil pollution
Pathogenic microbes
Environmental carcinogens
Perspectives
References

CHAPTER 5 Cancer stem cells—Challenges for cancer therapies
Rashi Arora, Apoorva Uboveja, and Rama Kadamb

Introduction
The identification of the CSCs
CSCs in tumorigenesis models
Biology of CSCs
Challenges posed by CSCs in cancer therapies
Ambiguity of the CSC markers
Crosstalk among the regulatory pathways
CSC-mediated tumor dormancy
Enhanced drug efflux activity of CSCs
Increased DNA repair in CSC’s
Enhanced autophagy and mitophagy in CSC’s
Suppressed ferroptosis in CSCs
Metastatic potential of CSC’s
Hypoxic adaptation
CSCs generate a tumor supporting niche
Epigenetic regulation
Perspective
References

CHAPTER 6 Carving a therapeutic niche for metastatic cancer: Opportunities and challenges
Sireesha V. Garimella, Rahul Roy, Siri Chandana Gampa, and Santhi Latha Pandrangi

Introduction
Hallmarks of cancer
History of metastasis
Mechanism of metastasis
Challenges for therapy of metastasis
Conclusion
References

SECTION 2 Epigenetics and its importance in cancer therapies

CHAPTER 7 An overview of epigenetics and cancer
Rajendra P. Pangeni

Role of epigenetics in normal and cancer cells
Epigenetics mechanism and their regulation on cancer
DNA methylation in cancer
Role of histone modifications in cancer
Chromatin remodeling in cancer
DNA methylation and histone methylation cross-talks
Role of epigenetic dysregulation of noncoding RNAs in cancer
Epigenetic dysregulation in cancer stem cells, a promise for therapeutic intervention
Epigenetics in the clinics: Prognostics, diagnostics, and therapeutic intervention for cancers
Harnessing epigenetics mechanism in prognosis and diagnosis of cancer
Epigenetic therapy: A targeted approach to cancer treatment
Advancements and innovation in epigenetic technologies in investigating mechanisms in cancer cells
Epigenetic profiling
Epigenome editing
Single-cell epigenomics
References

CHAPTER 8 Metabolic adaptation and epigenetic modulations: Unraveling tumor plasticity under variable tumor microenvironment
Jowana Obeid and Mehdi Damaghi

Introduction
Metabolic adaptation to TME
Metabolic microenvironment in solid tumors
TME altered metabolic pathways
Metabolic reprogramming via transcription factors in the TME
ROS and redox signaling in a harsh TME
Epigenetic and metabolic crosstalk in TME
DNA methylation
RNA methylation
Chromatin modifications
Noncoding RNA
Metabolic plasticity
Epigenetic modifications in shaping the TME
Epithelial-mesenchymal plasticity
Cancer cell dormancy
Intratumor heterogeneity leading to phenotypic variation
References

CHAPTER 9 Involvement of epigenetic modifications in cancer stem cells and chemoresistance
Prajakta Oak and Chitra Thakur

Tumor heterogeneity and drug resistance
Cancer stem cells: A new dimension to drug resistance
Reprogramming of cancer stem cells and epigenetic modifications
DNA methylation
Histone modifications
Histone methylation and demethylation
Histone acetylation and deacetylation
Noncoding RNAs
Micro-RNAs (miRNA)
Long noncoding RNAs (lncRNA)
RNA methylation
Epigenetic involvement in drug resistance
Therapeutic targeting of epigenetic alterations in cancers
DNMT inhibitors
Histone deacetylase (HDAC) inhibitors
Histone methyltransferase inhibitors
Combinatorial strategies for epigenetic therapeutics
References

CHAPTER 10 Cancer biomarkers: Where genetics meets epigenetics
Snehal Nirgude and Jennifer M. Kalish

Epigenetics in cancer biology
Histone modifications
Histone acetylation
Histone methylation
Histone PTMs as cancer biomarkers
DNA methylation
Chromatin remodeling complexes
Noncoding RNAs
miRNAs in cancer
miRNA-based therapeutic strategies
Conclusion
References

CHAPTER 11 Epigenetics approach in cancer treatment with focus on lung and breast cancer
Sayani Bhattacharjee

Introduction to epigenetics in breast and lung cancer
DNA methylation in breast and lung cancer
Chromatin remodeling and HDAC inhibition
Role of miRNAs as epigenetic biomarkers
Scope of epidrugs
Future directions
References

CHAPTER 12 Dietary components as epigenetic modifiers and their roles in cancer prevention
Chitra Thakur and Uttara Saran

Introduction
Epigenetic mechanisms and its importance in cancer
Crosstalk between dietary components and metabolism in epigenetic regulation
Types of dietary components and their role in epigenetics and chemoprevention
Dietary polyphenols
Epigallocatechin-gallate
Sulforaphane
Resveratrol
Curcumin
Quercetin
Genistein
Conclusion
References

SECTION 3 Nanomedicine targeting epigenetic machinery in cancer therapy

CHAPTER 13 Harnessing plant-derived biosynthetic nanomaterials for epigenetic modulation in cancer therapy
Ritu Karwasra, Kushagra Khanna, Shivani Bhardwaj, Nitin Sharma, Ashok K. Janakiraman, Ramkanth Sundarapandian, and Surender Singh

Introduction
Epigenetic modulation in cancer
Current approaches for epigenetic modulation in cancer therapy
Biosynthetic nanomaterials from plants
Plant-based nanomaterials used in cancer research
Epigenetic modulation by biosynthetic nanomaterials
Plant-derived nanoparticles for targeted delivery of epigenetic modifiers
Plant secondary metabolites as natural epigenetic modulators
Plant-based polymeric nanoparticles for sustained release of epigenetic drugs
Experimental evidence and preclinical studies
Clinical potential and future directions
Conclusion
References

CHAPTER 14 Nanotechnology-enhanced immunotherapy for cancer
Akshata R. Naik

Introduction
The fundamentals of the immune system
T-cell ontogeny
T-cell activation signals
Tumor immunology
Immune responses against tumors
Adoptive T-cell therapy for combating cancers
Immune checkpoints and their role in cancer immunotherapy
CTLA-4
PD-1/PD-L1 pathway
TIGIT
LAG3
Other therapies
Nanotechnological advances in immunotherapy
References

CHAPTER 15 Nanoparticles in metastatic cancer treatment
K.R. Manu, Ananya Kar, Pushparathinam Gopinath, Garima Gupta, Amirhossein Sahebkar, Prashant Kesharwani, and Rambabu Dandela

Introduction
Understanding metastasis in cancer
NPs for drug delivery
Fundamentals and rationale for using NPs in cancer treatment
Applications of NPs for drug deliverance
Targeted drug delivery methodologies
Passive targeting: EPR effect (enhanced permeability and retention)
Active targeting
Intracellular/intramolecular targeted therapies
Applications in metastatic cancer treatment
Conclusion and future perspectives
Acknowledgments
References

CHAPTER 16 Amine-terminated dendrimers: A novel method for diagnose, control and treatment of cancer
Yeganeh Modirrousta and Somaye Akbari

Introduction
A summary of amine-terminated dendrimers
The application of amine-terminated dendrimers in cancer
Diagnose
Treatment
Toxicity of dendrimers
Cytotoxicity
Hemolytic toxicity
Toxicity of dendrimers in the body
Conclusion and future trend
References

CHAPTER 17 Nanomedicine and epigenome: Possible health risks, benefits, and future perspectives
Nitin Verma, Komal Thapa, Neha Kanojia, Parul Sood, Jatin Kumar, and Kamal Dua

Introduction
Therapeutic implications of nanomaterial in nanomedicine
Diagnostic applications
Regenerative medicine
Therapy
Potential role of epigenetics in nanomedicine
Types of epigenetic modifications
In vitro and in vivo epigenetic modifications
Role of epigenetic alterations in the safety assessment of nanomaterials
Conclusion and future perspectives
References

CHAPTER 18 Smart cancer nanomedicine: Challenges and future opportunities
Moumita Roy

Introduction
Cancer treatment challenges
Nanotherapy and its challenges
Tumor microenvironment and nanotherapy action while targeting tumor physiology
pH-sensitive smart nanoparticles for targeting TME
Smart GSH, ROS, and Hypoxia-sensitive nanoparticles
Enzyme-responsive nanomaterials
Role of metal nanoparticles in cancer therapy
Gold nanoparticle
Silver nanoparticle
Platinum nanoparticles
Palladium nanoparticles
Nonnoble metal nanoparticle
Conclusion
Acknowledgments
References

Index