Breaking Tolerance to Pancreatic Cancer Unresponsiveness to Chemotherapy: Volume 5

Cover
BREAKING TOLERANCE
TO PANCREATIC
CANCER
UNRESPONSIVENESS
TO CHEMOTHERAPY
Copyright
Dedication
Contributors
About the Editor
About the Series Editor
Aims and Scope for Series ``Cancer Sensitizing Agents for Chemotherapy´´
Preface
1
Overview of Pancreatic Cancer Biology
	Conflict of Interest
		Introduction
		Pathogenesis and Molecular Biology
			Three Biological Stages of Cancer Development
			Initiation
			Clonal Expansion
		Oncogenesis
			KRAS
				Raf/Mitogen-Activated Protein Kinase (MAPK) Cascade
				Phosphoinositide 3-Kinase/ATK Cascade
				Nuclear Factor Kappa B Signaling Cascade
		Tumor Suppressor Genes
			CDKN2A
			TP53
			SMAD4
		Introduction to Local and Distant Microenvironments
		Familial Pancreatic Cancers
		Conclusions
		References
		Further Reading
2
Chemoresistance in Pancreatic Cancer: Emphasis on Age and Gender
	Conflict of Interest
		Introduction
		Pancreatic Cancer Incidences and Prognosis: Association of Age and Gender
		Chemoresistance: Association With Age and Gender
		Mechanisms Associated With Chemoresistance
		Factors Modulated in Various Age Groups
		Conclusion
		Acknowledgments
			References
3
EMT Contributes to Chemoresistance in Pancreatic Cancer
	Conflict of Interest
		Introduction
		Pancreatic Cancer Metastasis
		EMT Regulation in Pancreatic Cancers
			ZEB1
			SNAIL
			Twist
			PRRX1 (Paired Related Homeobox 1)
		Signaling Pathways Involved in the Regulation of EMT
			TGF-β
			Wnt/β-catenin
			Notch
			TNF-α
		EMT in Chemoresistance in Pancreatic Cancer
			5-Flurouracil Chemoresistance
			Gemcitabine Chemoresistance
		Role of EMT in Gemcitabine Resistance
		Promising Ways to Improving Gemcitabine Efficacy
		Conclusions and Future Perspectives
		Acknowledgments
			References
4
Pancreatic Cancer Resistance to Gemcitabine
	Conflict of Interest
	Introduction
	Gemcitabine Structure and Mechanism
	Gemcitabine Sensitivity
	Gemcitabine and Chemoresistance
	Role of Gemcitabine in Targeting Signaling Pathways
	Conclusion
	Acknowledgment
		References
5
Pancreatic Cancer and Possible Therapeutic Options
	Conflict of Interest
		Introduction
			Reasons Behind the Above Statistics?
			Brief Outline of Treatment
		Tumor-Node-Metastasis Staging and Clinical Classification
			Modalities for Evaluating TNM Staging
			Clinical Classification
		Treatment Options for Pancreatic Adenocarcinoma
			Localized Surgically Resectable Stage I and II Disease
			Adjuvant Therapy
				Gemcitabine and 5-Fluorouracil
				Gemcitabine and S-1
				Gemcitabine and Capecitabine
			Adjuvant Chemoradiation
				Gemcitabine Plus Nab-Paclitaxel
			Neoadjuvant Therapy
			Adjuvant Therapy in Borderline Removable Pancreatic Carcinoma
			Evidence Supporting Neoadjuvant Therapy
			FOLFIRINOX as Neoadjuvant Therapy
				NAC-GSL (Neoadjuvant Chemotherapy-Gemcitabine, S-1, LV)
		Metastatic Pancreatic Cancer: Treatment Options
			Early Period
			First-Line Therapies
				FOLFIRINOX
				PRODIGE-4/ACCORD-11 Trial
				Outcomes of PRODIGE-4/ACCORD-11 Trial
				Precautionary and Toxicity Reducing Strategies
				Gemcitabine Plus Nab-Paclitaxel
				The MPACT Trial
				When to Use FOLFIRINOX Versus Gemcitabine/Nab-paclitaxel?
				Clinical Parameters Indicating the Preferred Regimen
				Regimen Selection for Poor Performance Status Patients
			Second-Line Options
				5-FU Plus Oxaliplatin-Based Combination
			Nanoliposomal Irinotecan and 5-FU/Leucovorin Combination
				The NAPOLI-1 Trial
		Newer Treatment for Pancreatic Carcinoma
			KRAS Inhibitors
			RAF/MEK/ERK
			HER-2 Inhibitors
			Epidermal Growth Factor Receptor Inhibitors
			JAK/STAT Inhibitors
			Insulin-Like Growth Factor 1 Receptor Inhibitor
			Vascular Endothelial Growth Factor Receptor Inhibitors
		Tumor Stroma/Desmoplasia
			Transforming Growth Factor-β
			Platelet-Derived Growth Factor
			Hyaluronic Acid
			Matrix Metalloproteinase Inhibitors
			Hedgehog Inhibitors
		Conjugated Drugs
			Nab-Paclitaxel
			PEP02 (MM-398)
			Endo Tag-1
			Trastuzumab Emtansine
		Tumor Hypoxia
		Conclusions and Future Perspectives
		References
6
Curcumin and Genistein Enhance the Sensitivity of Pancreatic Cancer to Chemotherapy
	Conflict of Interest
		Introduction
		Chemotherapy for Pancreatic Cancer
		Tumor Microenvironment Developing Chemoresistance
		Curcumin Effecting as a chemo-sensitizer
		Genistein Effecting as a Chemo Sensitizer
		Signaling Cascades
			EGFR
			VEGF
			STAT Pathway
			Mitochondrial Pathway
			MiRNAs
			Notch Signaling Pathway
		Epigenome Changes
		Bioavailability
		Conclusion
		Acknowledgment
			References
7
Terpenoids as Potential Targeted Therapeutics of Pancreatic Cancer: Current Advances and Future Directions
	Conflict of Interest
		Introduction
		Pancreatic Cancer
			Risk Factor of Pancreatic Cancer
		Terpenoids
			Molecular Targets of Terpenoids in Pancreatic Cancer
				Terpenoids as NF-κB Signaling Inhibitors
				Terpenoids in the Regulation of Caspase Activity
				Terpenoids With Targeting DNA Damage
				Terpenoids Targeting Apoptotic Proteins
				Terpenoids With Differential Targets in Pancreatic Cancer
		Conclusion
		Acknowledgment
			References
			Further Reading
8
Small Molecules and Pancreatic Cancer Trials and Troubles
	Conflict of Interest
		Pancreatic Cancer: Causes and Treatments
			Causes and Prevention
			Therapeutic Treatments
		Pancreatic Cancer Resistance
			Causes of Treatment Resistance
			Combatting the Various Chemotherapy Resistance Pathways
		Pancreatic Cancer and Small Molecules
			General Overview of Small Molecules
			Heat Shock Proteins and HSP90 in Pancreatic Cancer
			HSP90 Inhibitors in Clinical Trials
			Acknowledgment
				References
9
Targeting the Epigenome as a Therapeutic Strategy for Pancreatic Tumors: DNA and Histone Modifying Enzymes
	Conflict of Interest
		Introduction
		DNA Methylation and Demethylation
		Histone Deacetylation and Acetylation
		Inactivating Histone Methylations
		Activating Histone Methylations
		Conclusions and Future Perspectives
		Acknowledgments
			References
10
Are Nanocarriers Effective for the Diagnosis and Treatment of Pancreatic Cancer?
	Conflict of Interest
		Current Status About Pancreatic Cancer
		Commonly Used Therapeutic Agents
			Chemotherapy
			Radiation Therapy
		Nanoscience and Nanotechnology
			Nanocarriers
			Polymeric Nanoparticle
			Polymeric Micelle
			Liposome
			Nanogel
			Mesoporous Inorganic Nanoparticle
			Metal Oxide Nanoparticle
			Inorganic Carbon Nanotubes
		Nanoparticles Used in Pancreatic Cancer
		References
11
Molecular Markers for Treatment Response and Toxicity of Gemcitabine
	Conflict of Interest
		Introduction
		Gemcitabine Transport and Metabolism of Action
			Dosing
			Toxicities with Gemitabine
		Candidate Genes Affecting Gemcitabine Therapy
		Neucleoside Transporter Genes
			SLC28 Family Gene Polymorphisms
			SLC29 Family
		Genes of Metabolizing Enzymes
			Cytidine Deaminase
			Deoxycytidine Kinase
			Deoxycytidylate Deaminase
			Cytidine Monophosphate Kinase 1
			Thymidylate Synthase
		Genes of Drug Targets
			Ribonucleotide Reductases 1
		Conclusions
		References
Index
	A
	B
	C
	D
	E
	F
	G
	H
	I
	J
	K
	L
	M
	N
	O
	P
	R
	S
	T
	U
	V
	W
	X
	Z
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