Knowledge about cancer genetics is rapidly expanding, and has implications for all aspects of cancer research and treatment, including molecular causation, diagnosis, prevention, screening, and treatment.

Additionally, while cancer genetics has traditionally focused on mutational events that have their primary effect within the cancer cell, recently the focus has widened, with evidence of the importance of epigenetic events and of cellular interactions in cancer development. The role of common genetic variation in determining the range of individual susceptibility within the population is increasingly recognized, and is now being widely addressed using information from the Human Genome Project. These new research directions will highlight determinants of cancer that lie outside the cancer cell, suggest new targets for intervention, and inform the design of strategies for prevention in groups at increased risk.

Today, the NCI is putting more and more money into research into the genetics of cancer. The very first of the NCI s stated research priorities is a project called The Cancer Genome Atlas. The Cancer Genome Atlas (TCGA) is a comprehensive and coordinated effort to accelerate the understanding of the molecular basis of cancer through the application of genome analysis technologies, including large-scale genome sequencing. The NCI and the NHGRI (National Human Genome Research Institute, where the series editor is employed) have each committed $50 million over three years to the TCGA Pilot Project.

This book proposes cover the latest findings in the genetics of male reproductive cancers; specifically cancers of the prostate and testes. The volume will cover the epidemiology of these cancers; model systems, pathology, molecular genetics, and inherited susceptibility."

This volume examines in detail the role of chronic inflammatory processes in the development of several types of cancer. Leading experts describe the latest results of molecular and cellular research on infection, cancer-related inflammation and tumorigenesis. Further, the clinical significance of these findings in preventing cancer progression and approaches to treating the diseases are discussed. Individual chapters cover cancer of the lung, colon, breast, brain, head and neck, pancreas, prostate, bladder, kidney, liver, cervix and skin as well as gastric cancer, sarcoma, lymphoma, leukemia and multiple myeloma.

Methylation of DNA at cytosine residues as well as post-translational modifications of histones, including phosphorylation, acetylation, methylation and ubiquitylation, contribute to the epigenetic information carried by chromatin. These changes play an important role in the regulation of gene expression by modulating the access of regulatory factors to the DNA. The use of a combination of biochemical, genetic and structural approaches has allowed demonstration of the role of chromatin structure in transcriptional control. The structure of nucleosomes has been elucidated and enzymes involved in DNA or histone modifications have been extensively characterized. Since deregulation of epigenetic marks has been reported in many cancers, a better understanding of the underlying molecular mechanisms bears the promise that new drug targets may soon be found. The newest developments in this quickly developing field are presented in this book.

The previous volume of this series on soft tissue sarcomas highlighted the importance of the multidisciplinary approach to treatment, the focus of which is continued in the present edition. Proper diagnosis and staging remain the cornerstone of the treatment strategy. Sophisticated histopathology techniques and growing consensus on grading systems have further increased the importance of the histopathologist in providing estimates of the prognosis of the patient as well as providing data for the planning of treatment strategy. The use of cytogenetics is relatively new in this field. This might enable the distinction of subgroups in specific histological tumor types. Furthermore, molecular biological studies not only help to reveal inherited predispositions and details in oncogenesis in tumor development, but they may also provide additional predictive factors for tumor behavior. Further data on treatment strategy will be provided by diagnostic imaging, a field in which the role of magnetic resonance imaging is rapidly developing. As far as actual treatment is concerned, surgery still provides the major chance for cure. In view of the endeavor to be as sparing as possible, the addition of radiotherapy to surgery is of utmost importance. Usually radiotherapy is given after surgery, but the optimal sequence of the two modalities still needs to be defined. The combined use of surgery with radiotherapy and/or chemotherapy does have an impact on wound healing.

A comprehensive review of the recent developments in DNA repair researchthat have potential for translational applications. The book explains in detail the various biologicalmechanisms by which cancer cells can circumvent anticancer therapy and limits its usefulness in patients. They also review the impact of such novel inhibitors of DNA repair mechanisms as methylguanine-DNA-methyltransferase. Also examined are inhibitors of other DNA repair enzymes such as PARP and DNA-PK. The book captures-for both cancer researchers and oncologists dealing with hallmark "relapse" or "drug resistance" phenomena on a daily basis-the many exciting new uses of DNA repair inhibitors, either alone or in combination with anticancer therapies.

Recent experimental evidence has made it increasingly clear In particular, this volume reviews the discrete steps involved that the properties of invasive, malignant cells during tumor in metastatic invasion: the interaction of invasive tumor cells development substantially impact on the host. This is under with extracellular matrices, the basement membrane, attach scored by a variety of biochemical properties of tumor cells ment to extracellular matrices, local proteolytic degradation during their differentiation and metastatic dissemination. of matrices, and the locomotion of invasive tumor cells These properties can be analyzed at different stages of tumor through such areas of localized degradation. The critical growth and progression and this volume explores the role of the cell surface in secondary tumor formation is characteristics of primary tumors as well as the shared reviewed as are important advances in the molecular biology characteristics of both primary and secondary tumors. of metastasis initiation and maintenance. Recent advances The primary tumor comes into existence following in the role of DNA methylation in the generation of tumor preneoplastic biochemical and cellular events that ultimate cell heterogeneity and tumor progression are also critically ly result in malignant transformation. Various aspects of summarized. Chapters in this volume also review molecular metabolism, predetermined by nutritional status, often play aspects of metastatic progression, and the use of the tech a basic role. Obesity, for example, is cancer-promoting. Cell nologies of DNA transfection and somatic cell fusion in the surface carbohydrates, cytoskeletal proteins, glycoproteins, exploration of molecular aspects of metastatic progression.

Resistance to chemotherapy, and especially multi-drug resistance, represents a significant barrier to the successful treatment of cancer. This multi-author volume brings together a wide range of up-to-date reviews on different aspects of our knowledge of drug-resistance mechanisms, written by experts in the different areas. Particular attention is paid to recently discovered mechanisms relating to oncogene expression and in particular to proteins involved in regulation and execution of apoptosis. Other important topics covered include DNA repair, topoisomerases, cell cycle control, oxygenation and vascularisation of tumours, LRP, intermediate filament proteins and low-level resistance. Recent developments in understanding the role of efflux pumps (P-170, MRP) in multi-drug resistance are also reviewed. This book will be useful to clinicians and scientists working in the areas of chemotherapy, drug resistance, DNA repair and apoptosis research.

This book is a rich source of information on biomarkers applicable to the pathology of neoplastic disorders of the brain. Thorough descriptions are provided of the techniques currently available for clinical and experimental evaluation of biomarkers in brain neoplasms, including in situ hybridization, array-based methods, methylation profiling, next-generation sequencing, and practical gene panels. Incorporation of multiple biomarkers in the development of molecular subgroups with biologic and therapeutic relevance is also discussed. A section on biobanking covers the equally important topic of optimal preservation of tissue and includes consideration of ethical considerations raised by the use of tissue obtained in clinical settings. The closing section discusses the major categories of neoplastic disorders involving the nervous system, with emphasis on diagnostic, prognostic, and predictive biomarkers used in the pathologic evaluation of different types of brain tumor.

This volume reviews the evolution of information regarding the epidemiology of DCIS and its modes of detection, as well as treatment options as a function of both clinical trial data and ongoing investigational therapeutic prospects. Several of the challenging and clinically-relevant scenarios of DCIS that appear in daily practice is discussed, including the difficulties of distinguishing "true" DCIS from borderline patterns of other breast diseases and the therapeutic implications of differentiating these various diagnoses. Particular attention is paid to pathologic evaluation of DCIS, including histologic patterns and the importance of margin evaluation/margin control. The text also explores the data regarding DCIS in medical research in hereditary susceptibility for breast cancer and race/ethnicity-associated disparities in breast cancer. Written by experts in the field, Ductal Carcinoma In Situ and Microinvasive/Borderline Breast Cancer is a comprehensive, state-of-the art review of the field, and serves as a valuable resource for clinicians, surgeons and researchers with an interest in breast cancer.

This, the second of two volumes on personalized medicine in lung cancer, touches upon the recent progress in targeted drug development based on genomics; emerging biomarkers and therapeutic targets such as EMT, cancer stem cells, and the tumor microenvironment; current personalized clinical management and radiation therapy for lung cancers; and the promise of epigenetics and next-generation sequencing for the advancements towards personalized therapy of lung cancer patients. With chapters on state-of-the-art therapies and technologies written by leading experts working to develop novel companion diagnosis tools for the personalized treatment of lung cancer patients, this volume brings readers up-to-date by presenting the current knowledge on the efforts to make personalized management of lung cancer patients a reality.

One of the major advances of the last decade concerning the treatment of patients with soft tissue sarcomas is that an increased number of patients are being discussed in multidisciplinary teams prior to the initial treatment. The present volume on soft tissue sarcomas in the series Cancer Treatment and Research reflects the multidisciplinary approach with a focus on recent developments. The availability of new histopathologic techniques has reduced the number of unclassified sarcomas and has furhter increased the importance of the histo pathologist in providing estimates of the prognosis of the patient as well as data for the planning of treatment strategy. Further data for this strategy will be provided by diagnostic imaging. In this field, the role of magnetic reson ance imaging has been further defined. Of utmost importance is the recent trend toward consensus in staging. The modification of the staging system of the American Joint Commission for Cancer Staging and End Results Report ing brings the possibility of a single staging system within reach in the next decade. As surgery still provides the only chance for cure, the importance of being the most sparing as possible is obvious. For this reason, radiotherapy has been applied with success. The introduction of relatively new radiation tech niques is therefore being observed with interest."

This volume provides an in-depth review of the data relating to the management of renal tumors as well as an updated description regarding pathologic and molecular classification of renal tumors. The neoplasms covered include clear cell carcinomas, papillary cancers, nonepithelial tumors, and other mass lesions that resemble tumors. The management of patients with renal cancer having localized or advanced disease is discussed. Surgical approaches for primary and metastatic tumors, symptom palliation, and systemic therapy for metastatic disease including immunotherapy and targeted approaches are discussed in detail.

Cutting-edge investigators review the current status of the entire field, from the biology of MMPs through the current clinical studies. The authors include many leading scientists from pharmaceutical companies who present all the latest concepts and results on the preferred design strategies for MMP inhibitors, their molecular mechanisms, and their substrates. In addition, they fully describe their personal research on specific MMP inhibitors, detailing vanguard design strategies, their in vitro activity, the outcome of animal model studies and, where available, their toxicology, safety, efficacy in human clinical trials.
Comprehensive and state-of-the-art, Matrix Metalloproteinase Inhibitors in Cancer Therapy offers basic and clinical investigators alike a richly informative summary of all the latest research on these powerful new drugs, and their high promise as emerging cancer therapeutics.

Heme oxygenase is rapidly taking its place as the centerpiece of multiple inter acting metabolic systems. Only 25 years ago heme oxygenase and its metabolic prod ucts appeared to be merely a simple metabolic system-one substrate, heme; one enzyme, heme oxygenase; and one set of products, iron to be recycled, and bilirubin and carbon monoxide to be disposed. From a group of about 25 people in 1974, as judged by attendance at various Gordon conferences, heme oxygenase has, in the year 2000, attracted working scientists-and clinicians I might add-by the hundreds and has produced referenced publications by the thousands. It is well-deserved attention. Heme oxygenase system is now similar to the metabolic networks surrounding glucose in those complex maps of glycolytic and non-glycolytic metabolic pathways, which we had to memorize as students. The relevance of heme oxygenase to regulatory biology was recognized many years ago, but the work conducted over the past five years has created a new wave of emphasis focusing on genetic manipulation to alter heme oxygenase gene expression, the regulatory actions of heme oxygenase products including carbon monoxide, and the significance of changes in the heme oxygenase system. The physiological and pathological relevance of heme oxygenase in the brain, heart, liver, bone marrow, organ transplant, lung and kidney, opens many areas of investigation in various dis ciplines. Advances in the pharmacology of bilirubin and its ability as an antioxidant have provided a new avenue in clinical research.

Cancer stem cells werehave originally been identified in leukemia and later in several solid tumor types. They have very different properties from the bulk of the tumor, as they divide much more slowly and have very efficient drug- resistance mechanisms. Current treatments might largely spare cancer stem cells, thus leading to tumor recurrence and metastasis. The recent identification of growth and differentiation pathways responsible for cancer stem cell proliferation and survival will help in the discovery identification of novel therapeutic targets. Developing selective drugs against cancer stem cells offers great therapeutic opportunities but also provides for major challenges regarding preclinical models, therapeutic windows, and clinical study end points.

Molecular Pathology of Gynecologic Cancer focuses on putting successful molecular strategies into practice for the treatment of gynecologic cancer. The volume begins with an explication of the editorsa (TM) hypothesis that cancer is mainly a disease of the cell cycle, based on the deregulation of the physiological process of cell reproduction. The following eleven chapters focus on specific issues in gynecologic cancers, including: a proposed model of ovarian serous carcinogenesis, molecular markers for ovarian epithelial cancer, an overview of the pathology of endometrial cancer, molecular genetic aspects of endometrial carcinoma and cervical cancer, a natural history of Human Papilloma Virus (HPV) as it relates to cervical cancer, and hereditary issues in gynecologic cancers. The concluding chapter proposes and outlines a holistic approach to the treatment of female cancer patients. This new volume in Humanaa (TM)s Current Clinical Oncologya"[ series will be necessary reading for clinicians and experimental researchers alike.

We are currently experiencing a fundamental shift in the way in which we approach the characterization of cancer. Never before has the make up of cancer tissues and individual cells been so exhaustively researched and char- terized. We are now capable of producing molecular "fingerprints" that ch- acterize the expression of all known and unknown genes within tumors and their surrounding tissues. More than 30,000 different genes may be measured in each patient's tumor in a single experiment. Simultaneously, novel therapies that exploit the molecular roadmap have been developed and are now being offered to patients. These novel agents, such as Glivec, Herceptin, Iressa, and others, specifically target individual genes within tumors and can produce d- matic responses in some patients. These drugs are only the forerunners of a coming tidal wave of novel therapeutics that individually target specific m- ecules within cancer cells-more than 300 such agents are currently in phase I or II clinical trials. This is an exciting time for cancer specialists and patients alike. However, if we have learned anything from the past 50 or more years of research into cancer, it is that Lord Beaverbrook, in founding the British national health service in the 1950s, was frighteningly prescient when he defined the primary goal of health care to be "Diagnosis, Diagnosis, Diag- sis. " Now, more than ever, it is essential that appropriate diagnostic methods and approaches are applied to the selection of patients for treatment.

The contents of Colorectal Cancer: Methods and Protocols aim to instruct investigators in all the key genetic, cellular, and molecular biological methods of analyzing colorectal tumors. The focused techniques and assays are described in sufficient detail to allow researchers to start an experiment on colon tumors and proceed from beginning to end as if the expert in the field who has performed these studies were guiding them at the bench. Of note, most of the chapters in this volume are written by those scientists who p- neered these methods and assays in their respective fields. The chapters in Colorectal Cancer: Methods and Protocols describe "state of the art" methods to analyze colorectal tumors, ranging from gross mic- dissection of specimens to specific molecular analyses. Included are coverages of mutational assays, instability testing, immunohistochemical assays, chro- somal studies, and gene expression analyses. The goal of our volume is to facilitate the performance of colorectal tumor biological experiments by investigators at various levels of training-from graduate students and postdoctoral fellows to principal investigators who desire to advance our understanding of colon cancer development.

In the past five years, a surprising and intense resurgence in interest in vitamins and other micronutrients and their role in health and dis ease has occurred. The recognition has emerged that vitamins not only are essential for life .in that severe nutritional deficiencies occur in their absence, but that these compounds may also serve as natural inhibitors of cancer. Synthetic alterations of the basic vitamin A mole cule have also resulted in the production of compounds that are more potent as anticancer agents than the natural substance and may have substantial therapeutic activity as well. Whether other vita mins can be changed or altered to produce a better anticancer effect than the native compound has been little explored to date, but should be a fruitful pursuit for future study. In our concluding remarks to the First International Conference in 1982, we speculated that rapid advances in our understanding of vi tamins would occur in the next few years and that large-scale inter vention trials of vitamins as preventive agents in defined human pop ulations would be started. This anticipated generation of data on vitamins and their interactions has proceeded rapidly and the impor tance of interactions between vitamins and other micronutrients in the prevention setting has become better appreciated. Currently, more than 25 intervention trials with a variety of target populations using vitamins and other micronutrients have been started, but it re mains too early for meaningful analysis of the results to date."

This volume began with an invitation from the publishers to edit a volume of EXS on Cancer. This invitation undoubtedly derived from my articles in Cellular and Molecular Life Sciences in 2002 and 2003 on the relationships between the morphology, aetiology and pathogenesis of tumours, especially in relation to genetic instability. After many years of teaching the theories of c- cer in undergraduate medical school courses, it seemed to me that the variably chaotic histopathologic features of tumours parallel in some way, the variably unstable genomes of tumour cells, which were being discovered in the 1990s. Thus the title of the volume has come to include morphology, carcinogenesis and genetic instability. The invitation came while I was working with Herrn Dr. med. Hubertus Jersmann (MD Dusseldorf, PhD, now Senior Lecturer in Medicine of the University of Adelaide) and Professor Brian Coghlan (Emeritus Professor of German, the University of Adelaide), on the work of the nineteenth century cancer pathologists, especially David Paul von Hansemann (1858-1920). With the delivery of the manuscripts from the authors of the chapters, it became obvious that a background chapter for the volume could include some of the material which we had "uncovered" together. Because of this, chapter 1 is authored by the three of us, and the "new" material figures prominently.

Molecular biology has rapidly advanced since the discovery of the basic flow of information in life, from DNA to RNA to proteins. While there are several important and interesting exceptions to this general flow of information, the importance of these biological macromolecules in dictating the phenotypic nature of living creatures in health and disease is paramount. In the last one and a half decades, and particularly after the completion of the Human Genome Project, there has been an explosion of technologies that allow the broad characterization of these macromolecules in physiology, and the perturbations to these macromolecules that occur in diseases such as cancer. In this volume, we will explore the modern approaches used to characterize these macromolecules in an unbiased, systematic way. Such technologies are rapidly advancing our knowledge of the coordinated and complicated changes that occur during carcinogenesis, and are providing vital information that, when correctly interpreted by biostatistical/bioinformatics analyses, can be exploited for the prevention, diagnosis, and treatment of human cancers. The purpose of this volume is to provide an overview of modern molecular biological approaches to unbiased discovery in cancer research. Advances in molecular biology allowing unbiased analysis of changes in cancer initiation and progression will be overviewed. These include the strategies employed in modern genomics, gene expression analysis, and proteomics.

Liver Cancer, the inaugural volume in the M.D. Anderson Solid Tumor Oncology series, provides the general surgeon, surgical oncologist, and medical oncologist with the most up-to-date and current standard of multimodality care for hepatobiliary cancer. Surgical approaches, chemotherapy, immunotherapy, gene therapy, and radiotherapy are all presented, giving the practitioner a much needed, comprehensive perspective on all aspects of patient care. The MD Anderson Solid Tumor Oncology series features cutting-edge, indepth information of vital interest to all practitioners in today's captitated financial milieu. Providers must understand how their component of care interdigitates with the varied medical and surgical teams and apply multimodality approaches to their practice environments.