**Meet the editor**

Dr Philippe E. Spiess is an assistant professor with dual appointment in the department of Genitourinary Oncology at the Moffitt Cancer Center and the department of Urology at the University of South Florida in Tampa, Florida. Dr Spiess was born and raised in Montreal, Canada where he completed his urological training at Mc-Gill University. He subsequently completed his urologic

oncologic training at the M. D. Anderson Cancer Center in Houston, Texas. Dr Spiess has published over 80 peer reviewed scientific papers in urologic oncology in addition to being a nationally and internationally recognized expert in the management of genitourinary malignancies. He has dedicated much of his research efforts to optimizing the surgical management of locally advanced and locally recurrent prostate cancer. He currently sits on the NCCN Panel for bladder and penile cancer in addition to being the video section editor of the International Brazilian Journal of Urology.

Contents

**Preface IX** 

Chapter 2 **Effective Methodologies** 

Chapter 1 **Prostate Cancer: Essential Diagnostic** 

**Part 2 Methods in Cancer Biology 11** 

Chapter 3 **Prostate Cancer, the Long Search** 

**Part 3 Signaling Pathways 91** 

Heidi Schwarzenbach

Chapter 7 **TRP-Channels and Human** 

Chapter 5 **Signalling Pathways** 

**and Therapeutic Considerations 3**  Paul Bradley and Philippe E. Spiess

Makoto Aoshima and Kazuyoshi Yata

**for Etiologic and Therapeutic Factors:** 

**& Drug Discovery in Prostate Cancer 53**  Malin Åkerfelt, Ville Härmä and Matthias Nees

Thomas Tallberg and Faik Atroshi

Chapter 6 **Clinical Relevance of Circulating Nucleic Acids** 

**Prostate Carcinogenesis 133** 

**in Blood of Prostate Cancer Patients 115** 

V'yacheslav Lehen'kyi and Natalia Prevarskaya

Chapter 4 **Advanced Models for Target Validation** 

**for Statistical Inference on Microarray Studies 13** 

**Dietary Supplementation Avoiding Invasive Treatment 33** 

**and Gene Expression Profiles in Prostate Cancer 93** 

Sophia Marsella-Hatziieremia, Pamela McCall and Joanne Edwards

**Part 1 Introduction 1** 

## Contents


**Part 1 Introduction 1** 

	- **Part 2 Methods in Cancer Biology 11**
	- **Part 3 Signaling Pathways 91**

X Contents


Contents VII

Chapter 19 **Zinc Supplementation and Prostate Cancer 423**  Wong Pooi-Fong and AbuBakar Sazaly

> **and Treatment of Prostate Cancer 445** Sophia L. Maund and Scott D. Cramer

**Prostate Cancer Drug Discovery 463** Jorge A. R. Salvador and Vânia M. Moreira

**of Prostate Cancer Stem Cells 493**

Luis A. Espinoza, Christopher Albanese and Olga C. Rodriguez

Chapter 20 **The Role of Vitamin D in the Prevention** 

Chapter 21 **Highlights of Natural Products in**

Chapter 22 **The Potential Target Therapy** 


VI Contents

Chapter 8 **Epidermal Growth Factor Receptor (EGFR) Phosphorylation, Signaling and Trafficking in Prostate Cancer 143** Yao Huang and Yongchang Chang

Chapter 9 **Prostate Cancer Dephosphorylation Atlas 173**  Carmen Veríssima Ferreira, Renato Milani,

Eduardo Galembeck and Hiroshi Aoyama

Chapter 11 **Integrins as Determinants of Genetic Susceptibility, Tumour Behaviour and Their Potential** 

Chapter 10 **Modulation of One-Carbon Metabolism by**

**as Therapeutic Targets 243** 

Chapter 13 **MAP Kinases and Prostate Cancer 283**

Ricardo Paniagua and Mar Royuela

**Part 4 Drug Therapeutics/Biological Agents 303** 

**for Its Anti-Cancer Properties 305** Yin-Quan Tang and Shamala Devi Sekaran

Chapter 15 **Prostate Cancer Progression to Androgen Independent Disease: The Role of the Wnt/β-Catenin Pathway 321**

Chapter 16 **Prostate Carcinoma and Hot Flashes 369** 

Chapter 17 **Paradigm Shift in the Concept** 

Tsutomu Nishiyama

Chapter 18 **The Role of Cancer Stem Cells and** 

Mustafa Ozen and Serhat Sevli

Glenn Tisman

Chapter 12 **Cytotoxic Endonucleases:** 

Chapter 14 **Evaluation of Phyllanthus,** 

Willian Fernando Zambuzzi, Thomas Martin Halder,

**B Vitamins: Implications for Transformation and Progression of Prostate Cancer 191** 

James R. Marthick, Adele F. Holloway and Joanne L. Dickinson

**New Targets for Prostate Cancer Chemotherapy 267** Xiaoying Wang, Marina V. Mikhailova and Alexei G. Basnakian

Gonzalo Rodríguez-Berriguete, Benito Fraile, Laura Galvis,

Jacqueline R. Ha, Yu Hao D. Huang and Sujata Persad

Santiago Vilar-González and Alberto Pérez-Rozos

**of Hormonal Milieu of Prostate Cancer 389** 

**MicroRNAs in Human Prostate Cancer 411** 


Preface

In this textbook entitled Prostate Cancer – From Bench to Bedside we highlight many of the essential concepts and consideration needed in understanding pathophysiological premise of prostate cancer. The introductory chapter highlights the major clinical advances made in the diagnostic and therapeutic management of prostate cancer over the past decade. In subsequent sections, we discuss essential considerations in cancer biology and methodology followed by a comprehensive

Lastly, the final section of this textbook pertains to drug therapeutics and biological agents currently being utilized or developed in the management of prostate cancer.

As editor-in-chief of this textbook, I would like to acknowledge the significant efforts made by Mrs Marija Radja and the entire editorial team of InTech Open Access Publisher in the publishing of this work. Their significant effort is greatly appreciated and the high quality of this publication is a testament to their dedication to providing our readership with the highest quality scientific knowledge. I would like to dedicate this textbook to my ever loving family who has supported my medical career from the early days I was a young man studying medicine and urology in Montreal and Toronto up to the present day. They have provided me with so much love and support which could have only resulted in me pursuing a successful academic career. This textbook is as well dedicated to the loving memory of our prostate cancer patients worldwide who when faced with the adversity of an aggressive, life threatening malignancy demonstrated boundless courage and optimism positively impacting the lives of all those that surrounded them. You will never be forgotten in our hearts and our memories similarly, you have provided us with the important lesson that we simply can't accept that our current treatment armamentarium is adequate but rather that we must to do better in eradicating this potentially fatal malignancy. Let the discoveries and breakthroughs of

**Philippe E. Spiess,** Editor-In-Chief

USA

Assistant Professor, Dept of Genitourinary Oncology

H. Lee Moffitt Cancer Center,Tampa, Florida

review of genetics and signaling pathways essential in prostate carcinogenesis.

the past serve as an impetus that we can and should do better.

## Preface

In this textbook entitled Prostate Cancer – From Bench to Bedside we highlight many of the essential concepts and consideration needed in understanding pathophysiological premise of prostate cancer. The introductory chapter highlights the major clinical advances made in the diagnostic and therapeutic management of prostate cancer over the past decade. In subsequent sections, we discuss essential considerations in cancer biology and methodology followed by a comprehensive review of genetics and signaling pathways essential in prostate carcinogenesis.

Lastly, the final section of this textbook pertains to drug therapeutics and biological agents currently being utilized or developed in the management of prostate cancer.

As editor-in-chief of this textbook, I would like to acknowledge the significant efforts made by Mrs Marija Radja and the entire editorial team of InTech Open Access Publisher in the publishing of this work. Their significant effort is greatly appreciated and the high quality of this publication is a testament to their dedication to providing our readership with the highest quality scientific knowledge. I would like to dedicate this textbook to my ever loving family who has supported my medical career from the early days I was a young man studying medicine and urology in Montreal and Toronto up to the present day. They have provided me with so much love and support which could have only resulted in me pursuing a successful academic career. This textbook is as well dedicated to the loving memory of our prostate cancer patients worldwide who when faced with the adversity of an aggressive, life threatening malignancy demonstrated boundless courage and optimism positively impacting the lives of all those that surrounded them. You will never be forgotten in our hearts and our memories similarly, you have provided us with the important lesson that we simply can't accept that our current treatment armamentarium is adequate but rather that we must to do better in eradicating this potentially fatal malignancy. Let the discoveries and breakthroughs of the past serve as an impetus that we can and should do better.

> **Philippe E. Spiess,** Editor-In-Chief Assistant Professor, Dept of Genitourinary Oncology H. Lee Moffitt Cancer Center,Tampa, Florida USA

**Scott Eggener, M.D.**  Assistant Professor, Department of Urology, University of Chicago, Chicago USA

#### **Vladimir Mourariev, M.D., Ph.D**. Department of Urology, University of Cincinnati, Ohio USA

#### **Matthew Biagioli, M.D**.

Assistant Professor, Department of Radiation Oncology, Moffitt Cancer Center, Tampa USA

#### **Kevin Zorn, M.D**.

Assistant Professor, Department of Urology, Universite de Montreal, Montreal Canada

#### **Shahrokh Shariat, M.D., Ph.D**.

Associate Professor, Department of Urology, Weill Cornell Medical Center, New York USA

#### **Dr Alejandro Rodriguez**

Assistant Professor, Department of Urology, University of South Florida, Tampa USA

X Preface

**Scott Eggener, M.D.** 

**Matthew Biagioli, M.D**.

**Kevin Zorn, M.D**.

Moffitt Cancer Center, Tampa

Universite de Montreal, Montreal

**Shahrokh Shariat, M.D., Ph.D**.

**Dr Alejandro Rodriguez**

USA

USA

USA

Canada

USA

USA

University of Chicago, Chicago

**Vladimir Mourariev, M.D., Ph.D**.

Assistant Professor, Department of Urology,

Assistant Professor, Department of Urology,

Associate Professor, Department of Urology, Weill Cornell Medical Center, New York

Assistant Professor, Department of Urology,

University of South Florida, Tampa

Department of Urology, University of Cincinnati, Ohio

Assistant Professor, Department of Radiation Oncology,

**Part 1** 

**Introduction** 
