Prostate Cancer: Advancements in the Pathogenesis, Diagnosis and Personalized Therapy

Preface
Contents
About the Editors
Part I: Recent Advances in Prostate Cancer Etiology and Pathogenesis
	Chapter 1: Prostate Cancer: Epidemiology, Etiology, Pathogenesis, and Risk Factors
		1 Epidemiology
		2 Etiology
		3 Prostate Physiology
			3.1 Stroma-Epithelium Interaction
		4 Sex Hormone Signaling Pathways
		5 Sex Hormone Levels in Prostatic Tissue
		6 Sex Hormones in Hyperplastic and Malignant Prostatic Tissue
		7 Cellular Metabolic Pathways and the Development of Prostate Cancer
		8 Risk Factors
			8.1 Hereditary Factors and Ethnicity
			8.2 Infections
			8.3 Diet
		9 Conclusion
		References
	Chapter 2: Genetic Susceptibility to Prostate Cancer
		1 Germline Mutations in Prostate Cancer
			1.1 BRCA1 and BRCA2
			1.2 Checkpoint Kinase 2 (CHEK2)
			1.3 Ataxia-Telangiectasia Mutated (ATM) Gene
			1.4 Partner and Localizer of BRCA2 (PALB2)
			1.5 The Mismatch Repair Genes
		2 Polygenic Risk Scoring in Prostate Cancer Susceptibility
		3 Guidelines
		4 Conclusions
		References
	Chapter 3: Basic Insights into Tumor Microenvironment in Prostate Cancer
		1 Prostate Anatomy and Function—Link to Oncogenesis
		2 Microenvironment in Tumor Progression
			2.1 TME in Unique Metabolic Template of Prostate Cancer
			2.2 Stromal Cells in TME Shaping
			2.3 Hypoxic Fluctuation and Prostate Cancer Spatial Heterogeneity
		3 TME and Prostate Cancer Metastasis Bone As a Choice
			3.1 Metabolic Impact on Prostate Cancer Metastasis
		4 Immune Interactions Within the TME
			4.1 Macrophages in Prostate Cancer Progression
			4.2 Neutrophils in the TME
			4.3 Mast Cells in the TME
			4.4 Myeloid-Derived Suppressor Cells
			4.5 T Cells and Immune Surveillance in Prostate Cancer
			4.6 Metabolic Reprogramming of Immune Cells
		5 Perspective
		References
	Chapter 4: Oxidative Stress, Redox Signaling, and Apoptosis in Prostate Cancer Development and Progression
		1 Introduction
		2 Xanthine Oxidase As a Source of Oxidative Stress in Prostate Cancer
		3 The Role of Oxidative Stress in the NF-κB Signaling Pathway in the Process of Carcinogenesis
		4 Apoptosis in the Pathogenesis of Prostate Cancer
		References
	Chapter 5: Epigenomics, Transcriptomics, and Translational Control in Prostate Cancer
		1 Epigenetics of Prostate Cancer
		2 The Types of Epigenetic Changes That Can Happen in Prostate Cancer
			2.1 The Role of DNA Methylation in Prostate Cancer Development and Progression
			2.2 The Role of Histone Modification in Prostate Cancer Development and Progression
			2.3 The Role of miRNA and Small Noncoding RNAs in Prostate Cancer Development and Progression
			2.4 What Are the Implications of Epigenetics in Prostate Cancer?
		3 The Role of Transcriptomics in Prostate Cancer
		4 The Role of Translational Control in Prostate Cancer
		5 Conclusion
		References
	Chapter 6: Metabolic Reprogramming As a Prostate Cancer Hallmark
		1 Introduction to Metabolic Rewiring in Cancer: Unveiling the Intricacies of Cellular Transformation
		2 Metabolic Adaptations in Prostate Cancer: From Mystery to Mastery
			2.1 Disturbance of the Zinc–Citrate Relationship
			2.2 Alteration of Lipid Metabolism
			2.3 The Role of One-Carbon Metabolism
		3 Conclusion
		References
Part II: An Integrative Approach in Prostate Cancer Diagnostics
	Chapter 7: Diagnostic, Prognostic and Theranostic Potential of miRNAs in Prostate Cancer
		1 Introduction
			1.1 Dysregulation of miRNAs in Cancer
			1.2 The Role of miRNAs As Potential Diagnostic and Prognostic Biomarkers for Prostate Cancer
				1.2.1 miRNAs Associated with AR Functions
				1.2.2 miRNAs Associated with Cell Cycle, Proliferation and Apoptosis
				1.2.3 Perspectives of miRNAs Multipanel Approach
			1.3 miRNAs Regulating GSTP1 Expression in Prostate Cancer
			1.4 Theranostic Potential of miRNAs in Prostate Cancer
		2 Perspectives in Prostate Cancer Diagnosis and Treatment
		References
	Chapter 8: Diagnostic Approaches of Prostate Cancer: When Is a Biopsy Required?
		1 Introduction
		2 Symptoms and Signs
		3 Screening
			3.1 Physical Examination
			3.2 Laboratory Findings
				3.2.1 PSA
					3.2.1.1 PSA Density
					3.2.1.2 fPSA/tPSA
			3.3 Other Biomarkers
		4 Imaging in Prostate Cancer
			4.1 Multiparametric MR (mpMR) in Prostate Cancer
			4.2 PI-RADS (The Prostate Imaging Reporting and Data System)
		5 Prostate Biopsy
			5.1 When Is Prostate Biopsy Required?
				5.1.1 Indications for Prostate Biopsy
				5.1.2 The Role of mpMRI in Prostate Biopsy
				5.1.3 mpMRI Offers Several Advantages in the Diagnostic Process
		References
	Chapter 9: Histopathological and Molecular Markers in the Assessment of Prostate Cancer Aggressivity
		1 Histopathological Indicators of Prostate Cancer Aggressiveness
			1.1 Gleason Grading
			1.2 Prognostic Impact of High-Grade Prostatic Cancer
			1.3 Tumor Volume in Prostate Biopsy
			1.4 Prostate Cancer Risk Groups
			1.5 Perineural Invasion
			1.6 Highly Aggressive Types of Prostatic Cancer
			1.7 Intraductal Carcinoma
			1.8 Ductal Adenocarcinoma
			1.9 Prostate Cancer and Neuroendocrine Differentiation
		2 Molecular Markers in Aggressive Prostate Cancer
			2.1 Cell Cycle Proteins in Aggressive Prostate Cancer
				2.1.1 p53
				2.1.2 PTEN
				2.1.3 Bcl-2
				2.1.4 Ki-67
			2.2 EZH2
			2.3 CXCR4
			2.4 Stemness Markers in Aggressive Prostate Cancer
				2.4.1 CD117
				2.4.2 CD133
				2.4.3 CD44
		References
	Chapter 10: Tumor Markers in Early Detection and Monitoring of Prostate Cancer: Recent Advances
		1 Introduction
			1.1 Novel Urinary Diagnosing and Monitoring Biomarkers
			1.2 Novel Blood Biomarkers
			1.3 Novel Tissue and Metabolomics Biomarkers
			1.4 Exosomes
			1.5 Nanomaterial Biosensors
			1.6 Future Perspective in Precision Medicine Approach Toward Early Detection and Monitoring of PC
		References
	Chapter 11: Biological Markers of Therapeutic Response in Prostate Cancer
		1 Introduction
		2 Biomarkers for Localized Prostate Cancer Considering Treatment
			2.1 Oncotype DX
			2.2 Decipher
			2.3 ProMark
			2.4 Prolaris
		3 Biomarkers for Localized Prostate Cancer in Post-prostatectomy Setting Considering Adjuvant Therapy
			3.1 Decipher
			3.2 OncotypeDx
			3.3 Ki-67
			3.4 PORTOS
		4 Biomarkers in Metastatic Prostate Cancer
			4.1 TP53, RB1, PTEN and SPOP Gene Mutations
			4.2 Molecular Subclassification: Luminal A, Luminal B and Basal Subtypes of Prostate Cancer
			4.3 Circulating Tumour Cells (CTCs)
			4.4 AR-V7
			4.5 Biomarkers of Homologous Recombination (HR) DNA Repair Defect
			4.6 PSMA
		5 Conclusion
		References
Part III: Current Treatment Options and Monitoring of Prostate Cancer
	Chapter 12: Surgical Treatment of Prostate Cancer
		1 Radical Retropubic Prostatectomy
		2 Radical Perineal Prostatectomy
		3 Laparoscopic Radical Prostatectomy
			3.1 Extraperitoneal Laparoscopic Radical Prostatectomy
			3.2 Laparoscopic Radical Prostatectomy with Lymphadenectomy
		4 Robot-Assisted Radical Prostatectomy
		References
	Chapter 13: Robot-Assisted Laparoscopic Radical Prostatectomy
		1 Introduction
		2 Perioperative, Functional, and Oncologic Outcomes
		3 Hospital Cost
		4 Summary
		References
	Chapter 14: The Use of Apheresis in Personalized Cell-Mediated Treatment of Prostate Cancer
		1 Apheresis: A Brief Synopsis with Systematic Consideration
			1.1 Apheretic Donation
			1.2 Therapeutic Apheresis
				1.2.1 Therapeutic Plasma Exchange
				1.2.2 Selective TPE for ABO-Incompatible Kidney Transplant
				1.2.3 “Multimanner” Apheresis
				1.2.4 Therapeutic Apheresis in Cancer Disease
				1.2.5 Therapeutic Cytapheresis
		2 Apheretic Stem and Mononuclear Cell Collection
			2.1 Stem Cell Harvesting: A Preclinical Data Summary
			2.2 Mononuclear Cell Harvesting: Designed for Anticancer Therapy
				2.2.1 Anticancer Vaccines: DC-Based Immunotherapy
				2.2.2 Immunotherapy Using CAR-T Cell
		3 Adverse Events of Apheresis and Cell-Based Hemobiotherapy
		4 Author Opinion
		5 Conclusions
		References
	Chapter 15: Hormone Therapy for Advanced Prostate Cancer
		1 Introduction
			1.1 Prostate Cancer Statistics, Diagnostics, and Pathogenesis
			1.2 The Hypothalamic-Pituitary-Gonadal Axis and Mechanisms of Androgen Action
			1.3 Testosterone Structure and Function
			1.4 The Androgen Receptor (AR) Structure
		2 Hormonal Therapy of Prostate Cancer
			2.1 Treatment Options of Particular Hormone Therapies Related to Target Sites
			2.2 LHRH Agonists in Prostate Cancer Treatment
			2.3 Prostate Cancer Hormone Treatment by LHRH Antagonists
			2.4 Prostate Cancer Hormone Treatment by Testosterone and Pregnenolone Synthesis Inhibitors
			2.5 Prostate Cancer Hormone Treatment by 17α-Hydroxylase Inhibitors
			2.6 Prostate Cancer Hormone Treatment by Antiandrogens-Androgen Receptor Blockers
			2.7 Prostate Cancer Hormone Treatment by Estrogens
			2.8 Castration-Sensitive, Castration-Resistant, and Hormone-Refractory Prostate Cancer
		3 The Therapeutic Principles of Androgen Deprivation Therapy (ADT)
			3.1 Bipolar Androgen Therapy
		4 Hormone Resistant Prostate Cancer HRPC
			4.1 Designs of Clinical Studies in Monitoring the Clinical Outcome of Hormone Therapy
		5 Adverse Effects of Hormone Therapy
		6 Conclusion
		References
	Chapter 16: Perspectives of Immunotherapy in Prostate Cancer
		1 Introduction
		2 Immunotherapy in Prostate Cancer
		3 Types of Immunotherapies
		4 Challenges and Future Directions
	Chapter 17: Pharmacogenomics and Precision Therapy in Prostate Cancer: Challenges and Perspectives
		1 Introduction
		2 Definition of Pharmacogenetics, Pharmacogenomics, and Precision Therapy Concept
		3 Pharmacogenomics and Precision Therapy in Oncology
		4 Driver Mutations and Targeted Therapies
			4.1 Monoclonal Antibodies
			4.2 Small Molecule Inhibitors
			4.3 Research Directions and Clinical Trials in Precision Oncology
		5 Pharmacogenomics and Precision Therapy in Prostate Cancer
		6 Targeted Therapies for Advanced Prostate Cancer
			6.1 Immune Checkpoint Inhibitors
			6.2 Poly-ADP Ribose Polymerase Inhibitors
				6.2.1 Diversity of HRR Pharmacogenomic Biomarkers Concerning PARP Inhibition
				6.2.2 Mechanisms of Resistance to PARP Inhibitors
			6.3 Sipuleucel-T Cellular Immunotherapy
			6.4 Targeted Radiotherapy
				6.4.1 Radium-223 Dichloride
				6.4.2 177Lu-PSMA-617
			6.5 Vascular Targeted Therapy
		7 Future Perspectives of Precision Therapy in Prostate Cancer
		References
	Chapter 18: Stereotactic Radiotherapy in the Treatment of Prostate Cancer
		1 Introduction
			1.1 History
			1.2 Terminology
				1.2.1 SRS and SRT
				1.2.2 SBRT and SABRT
		2 Immunology
		3 Machine for SBRT Radiotherapy
		4 Indications for SBRT in Prostate Cancer
			4.1 Doses
			4.2 Preforming
			4.3 Technic of Radiotherapy
		5 Toxicity
		6 Follow-Up
		7 Efficacy of SBRT
		References
	Chapter 19: Treatment of Castration-Resistant Prostate Cancer
		1 Introduction
		2 Clinical Features of the Disease
			2.1 Castration-Resistant Prostate Cancer
		3 Therapeutic Approach and New Perspectives
			3.1 Androgen Deprivation Therapy (ADT)
				3.1.1 Inhibition of Testosterone Secretion
				3.1.2 Inhibition of Testosterone Action
			3.2 New Perspectives
		References