Preface

**Section 3 Management of Metastatic/Advanced Renal Tumor 131**

Chapter 9 **Current Perspectives in Metastatic Renal Cell Carcinoma Treatment: The Role of Targeted Therapies 145** V. Michalaki, M. Balafouta, D. Voros and C. Gennatas

**Carcinoma 157**

**VI** Contents

Mirjana Rajer

Chapter 10 **New Systemic Treatment Approaches for Metastatic Renal Cell**

Chapter 11 **Changing Mechanisms of Action as a Strategy for Sequential**

Thean Hsiang Tan, Sina Vatandoust and Michail Charakidis

**Targeted Therapy of Metastatic Renal-Cell Carcinoma 187**

Chapter 8 **Surgical and Oncological Results of Treatment of Metastases of**

Archil Chkhotua, Laurent Managadze and Ambrosi Pertia

**Renal Cell Carcinoma to the Contralateral Adrenal Gland 133**

Renal cell carcinoma (RCC) is the most common type (>80%) of kidney cancer that arises from the cells of the renal tubules. Although RCC is relatively rare and only represents approximately 3% of all adult cancer, an alarming increase in incidence has been observed in the past five decades. Worldwide, approximately 150,000 new cases are diagnosed with RCC each year, and around 95,000 affected people die from the disease annually. While patients with early, localized RCC have a good prognosis, those with advanced disease (metastatic RCC) do not respond to most traditional therapeutic approaches, and survival for such patients is often less than 1 year. Unfortunately, most patients are diagnosed with advanced RCC, which causes anti-RCC treatment more challenging. Even so, with the advent and improvement of edge-cutting biomedical techniques, a significant amount of new information concerning the epidemiology, molecular genetics, immunologic char‐ acteristics, and therapy for patients with these tumors has appeared. Through the integration of molecular-based technologies, systematic tissue procurement and medical informatics, research data can rapidly be translated into useful diagnostic and treatment strategies. In fact, the increasing understanding of the pathogenesis of RCC has led to the development of novel targeted agents. New anti-RCC drugs have now been approved and commercially available, some potential drugs are also under clinical trial.

Here, to provide urologist and kidney cancer researchers with updated knowledge of RCC biolo‐ gy, current treatment practices, and novel treatment strategies, experts from all over the world, combining their our experience, explored and reviewed the latest developments in molecular ge‐ netics, surgery, and novel therapeutic strategies for renal tumors and organized into this book Renal Tumor. This book contains 11 chapters in three parts, covering the roles of partial nephrec‐ tomy, radical nephrectomy, and laparoscopy, as well as the latest developments in molecular ge‐ netics and immune dysfunction, signal transduction, and anti-RCC drugs associated with the diseases. Also discussed are imaging and screening for RCC, its diagnosis, paraneoplastic syn‐ dromes, and prognostic factors in metastatic disease.

It is hoped that Renal Tumor will offer all physicians treating kidney cancer as well as researchers current practical knowledge about the nature, diagnosis, prognosis, management and treatment of this difficult disease.

Finally, thanks to all the authors who have contributed their valuable time to write all the chap‐ ters. Without their efforts and dedication, the formation of this book would never be possible.

> **Jindong Chen, Ph.D.** Research Associate Professor, Co-director, Kidney Cancer Research Laboratory, Department of Urology University of Rochester Medical Center, Rochester, NY, USA

**Section 1**

**Molecular Biology of Renal Tumor**

**Molecular Biology of Renal Tumor**

**Chapter 1**

**Genetics of Renal Tumors**

http://dx.doi.org/10.5772/54588

obtained for diagnostics/therapeutics.

**1. Introduction**

Ryoiti Kiyama, Yun Zhu and Tei-ichiro Aoyagi

Additional information is available at the end of the chapter

Kidney and urinary tract cancers accounted for a total of 16936 cases and 6764 deaths in 2007 in Japan (Matsuda et al., 2012), which is roughly 2% of all cancers. Renal cell carcinoma (RCC) is the most common type of kidney cancer, and is classified into three major subtypes, clear cell RCC, papillary RCC and chromophobe RCC, representing 80, 10, and 5% of all RCCs, and the majority of renal tumors are sporadic although 2-4% are hereditary (Hagenkord et al., 2011).

A number of genes have been studied in association with renal tumors, including those involved in tumorigenesis, and the progression and outcome of the cancer, by means of mutational searches, gene expression profiling, proteomics/metabolomics and pathological/ clinical studies. The genes can be classified into several categories, such as familial, sporadic, epigenetic and quantitative, depending on the timing of their expression, and the factors affecting their effects, such as microRNA (miRNA) and metabolites have emerged. Since tumorigenesis is believed to be initiated with genetic/epigenetic modulations of at least several genes, but not a single gene alone, the balance among these cancer-related genes is considered to be more important than the contribution of a dramatic change caused by a single gene. Thus, an extensive and competitive search for oncogenes and tumor suppressor genes based on the search for their mutations was immediately accompanied by the search for interacting proteins/factors at the mutation sites. This indicates that lineages of gene functions, or signaling pathways, are important to understanding tumorigenesis, as well as the progression and outcome of the cancer. Although such pathways are not fully understood, it is important to summarize the latest knowledge of genes and their functions in terms of the coordinated functions of genes to achieve a basic understanding of cancer and to use the information

Here, we summarize and discuss the genes associated with renal tumors (Section 2) and then show one of them, *Kank1*, from gene-function networks or signaling pathways (Section 3). We

> © 2013 Kiyama et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2013 Kiyama et al.; licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
