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This book describes the changing role of pathology in aiding reproducible and accurate patient selection for predictive cancer therapy. Particular attention is given to the clinical application of cutting-edge cancer biomarkers to accurately select patients for targeted cancer therapy and how artificial intelligence can improve the precision of treatments. The advent and basis of predictive cancer care, the role of pathologists in translational cancer research, the analysis of cancer samples, the management of biopsy results, and the accuracy of biopsy results are also discussed. Precision Cancer Medicine: Role of the Pathologist details how pathologists can use the latest biomarkers and apply artificial intelligence technology in cancer diagnosis and management. It is also relevant to oncologists and medical practitioners involved in cancer management seeking an up-to-date resource on the topic.

This book integrates the disciplines of cancer pathology and epidemiology to provide a synergistic and complementary approach to understanding the molecular mechanisms of cancer. This book provides relevant information on the diagnostic, prognostic and predictive molecular pathology of cancer. Epidemiological studies, including descriptive epidemiology, risk factors and molecular mechanisms of disease inform on the etiology and progression of cancer. The text concentrates on major cancers that are currently prevalent and those for which substantial molecular, pathological and epidemiological data is available. Each section is designed to provide an overview of that cancer type in terms of basic biology, review the current epidemiological data surrounding that cancer type and provide information on common practices and challenges related to the molecular pathology of that cancer type. Several relevant techniques in molecular pathology, which facilitate diagnosis and treatment are also explored. Pathology and Epidemiology of Cancer provides a succinct and comprehensive overview of multiple cancer types to guide clinicians during patient care and to guide scientists for innovations in research. It represents an integral resource for pathologists, epidemiologists, medical students as well as translational, basic and clinical science researchers who are all working to progress the field of cancer in terms of diagnosis, treatment and prevention.

This book is directed primarily to advanced graduate and medical students, postdoctoral trainees, and established investigators having basic research interests in neoplasia. Its content is based in part on the lecture outlines and selected histopathology laboratory components of an advanced course entitled The Pathobiology of Experimental Animal and Human Neoplasia, developed by me for the Experimental Pathology Curriculum of the Department of Pathology at the Medical College of Virginia. In this regard, an effort has been made to integrate pathology with carcinogenesis, genetics, biochemistry, and cellular and molecular biology in order to present a comprehensive and current view of the neoplastic process. For focus, emphasis is mainly being placed on the neoplastic cells themselves, and not on associated host-mediated responses. It ishoped that this book will accomplish its purpose of providing students and researchers who already possess strong but diverse basic science backgrounds with unifying concepts in tumor pathobiology, so as to stimulate new research aimed at furthering our understanding of neoplastic disease. I wish to express my appreciation and heartfelt thanks to the authors, whose individual ranges of expertise and research experience clearly bring to their respective chapters unique perspectives that easily transcend any redundancy that may be present. In addition, I am grateful to Drs. George Vennart, Saul Kay, and Fred Meier, and to Ms. Connie Wilkerson of the Department of Pathology at MCV, for their helpful comments and their review of some of the material.

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.

This volume reviews our current knowledge concerning can­ Several chapters discuss the contributions of genetic asp­ cer growth and progression as it relates to the etiology of ects, metabolism, endocrine-related aspects and nutrition to human cancer. As emphasized in Volumes I-V of this series, cancer progression. Moreover, our current knowledge con­ neoplastic diseases are multistep maladies. There are many cerning urbanization factors, radiation, therapy-induced causes for the appearance of neoplastic diseases. Earlier neoplasms, environmentally induced neoplasms (e. g., chapters in the series have reviewed molecular and cellular mesotheliomas induced by asbestos) and malignant neo­ aspects of tumor initiation, promotion and progression to plasms in organ transplant recipients are summarized. the invasive and metastatic phenotype. Contributions to the The impact of AIDS on neoplasm development is re­ initiation and progression of neoplastic diseases are made by viewed from an epidemiologic perspective that explores mul­ natural features of the environment and by its contaminants tiple facets of immunity, infectious disease, sexual behavior and by nutritional factors. Neoplastic diseases show a dis­ and blood transfusion. Other chapters investigate the in­ tinct relationship to a variety of environmental stimuli and fluence of the host immune response in oncogenesis and the to diseases of a non-neoplastic nature. For example, familial relationship between atherosclerotic plaques and tumors.

It is widely recognized that the host response to tumor munotherapy of experimental metastases in animal systems progression is an important determinant in cancer growth which are beginning to be developed for ultimate clinical and progression. Indeed, as indicated in Volume I of this trials of human cancer metastasis. series, the process of cancer growth and progression, leading This volume explores a variety of host properties that to tumor invasion and metastasis, is dependent upon the influence tumor development including dormancy, regress­ complex, dynamic interactions between the properties of the ion, and recurrence. In addition, current knowledge of the tumor as well as the properties of the host. While Volume III response of the central nervous system to cancer, cardiac of this series reviews in great detail the influence of tumor and pulmonary complications, dermatologic effects and development on the host, this volume emphasizes the in­ hematologic complications of malignancies is presented. fluence of the host on tumor development. These host re­ The endocrine and metabolic function of cancer patients, as sponses include host anti-tumor immune reactivity, tumor well as the production of hormones by tumors is also review­ dormancy, cachexia, multiple endocrine and paraneoplastic ed.

Clinically accessible information for pathologists on the fast moving field of molecular pathology and oncology, addressing molecular and genetic approaches to the diagnosis and classification of tumors, predictive biomarkers for treatment response and disease progression. Recurrent in this series, summaries are provided of Key Features of tumor, Key molecular prognostic markers and therapeutic markers, Tumor suppressor genes, and Oncogenes. Topics include molecular pathology of: Breast, Gastrointestinal, Head and Neck, Genitourinary, Gynecologic, Hematopathology, Lung, Neuropathology, Pancreas/Biliary, and Sarcome.

but also the possibility of intervention in specific stages. In Human behavior, including stress and other factors, plays an important role in neoplasia, although too little is known addition, variables which affect cancer development as well on the reasons for such development. Carcinogens, which as some endogenous factors can be better delineated help initiate the neoplastic process, may be either synthetic through such investigations. The topics of this volume encompass premalignant non­ or naturally-occurring. Cancer causation may be ascribed to invasive lesions, species-specific aspects of carcinogenicity, certain chemicals, physical agents, radioactive materials, viruses, parasites, the genetic make-up of the organism, and radiation, viruses, a quantum theory of carinogenesis, onco­ bacteria. Humans, eumetazoan animals and vascular plants genes, and selected environmental carcinogens. are susceptible to the first six groups of cancer causes, whe­ reas the last group, bacteria, seems to affect only vascular plants. Neoplastic development may begin with impairment ofJmdy defenses by a toxic material (carcinogen) which acts as an initiator, followed by promotion and progression to an overt neoplastic state. Investigation of these processes Series Editor Volume Editor allows not only a better insight into the mechanism of action Hans E. Kaiser Elizabeth K. Weisburger vii ACKNOWLEDGEMENT Inspiration and encouragement for this wide ranging project on cancer distribution and dissemination from a comparative biological and clinical point of view, was given by my late friend E. H. Krokowski.

In the post-genomic era, cancer is a genetic disease. However, cancer genotype does not always equal cancer phenotype. Cancers with the same genetic abnormalities don't always behave the same. Understanding and eradicating cancers will require an appreciation for cancer's ecology. This book is the first to comprehensively explore and critically appraise cancer microenvironments and host interactions with an eye towards exploiting our understanding for new treatments. The team of contributors share amongst them impressive experiences at the laboratory bench and in the clinic. These physician-scientists have dedicated themselves to the tension between the urgency for cures and the technical challenges of discovery. The target audience includes clinical oncologists, clinical hematologists, research oncologists, research hematologists, immunologists, stem cell researchers, oncology and hematology fellows (trainees), oncology educators (graduate and undergraduate levels), and course book for graduate students and undergraduate students.

Transforming Growth Factor-B in Cancer Therapy, Volume II: Cancer Treatment and Therapy The chapters in this volume confer an abundance of knowledge about the current state ofour understanding oftransforming growth factor-B (TGF-B) in cancer treatment and therapy. Unlike several more traditional positive polypeptide growth factors that stim­ ulate cellular proliferation, the prototypical TGF-B is now known to inhibit the growth of most normal cell types, including those of epithelial and mesenchymal origin. However, there are examplesofcell types that can be stimulated by TGF-B under certain conditions. TGF-B also induces the accumulation of matrix molecules by stimulating their synthesis as well as inhibiting their degradation. Moreover, TGF-B induces apoptosis of certain cell types, thereby restricting their proliferation. OveractivityofTGF-~ has been linked to several diseases. For instance, the effect ofTGF-~ on matrix accumulation contributes to fibrotic conditions, like glomerulonephritis, lung fibrosis and liver cirrhosis (1). TGF-~ has a very complicated role in cancer that is only beginning to be understood.