In September 2005 an International Meeting on “Targeted Therapies in Cancer: Myth or Reality” was held in Milan. This successful Meeting was intended to represent a forum for scientists and clinicians working in cancer drug discovery and therapy to share their reflections and experiences on how the paradigm shift from empiricism to molecular targeted therapies is contributing to the translation of basic knowledge into new therapies for cancer patients. This book collects the contributions given by scientists and clinicians, from Academia and Industry, who participated to this Meeting.

We hope that this book contributes to improve our approach to cancer drug discovery and, ultimately, to find new, more efficacious and better tolerated drugs for cancer patients. It provides an overview of diverse approaches ranging from drug discovery to cellular therapy. Although this change in paradigm has been useful, its entry into the clinical arena was associates with unforeseen problems including the emergence of resistance, unexpected side effects and failures. Time is therefore ripe for a critical cultural reflection on the state of the art, prospects and limitations. Ultimately, is targeted therapy in cancer a myth or a reality?

Macrophages are a key component of the innate immune system and play an integral role in host defense and homeostasis. On one hand, these cells contribute to host defence by triggering inflammation, displaying microbicidal/tumoricidal properties, regulating the activation of adaptive immunity and promoting resolution of inflammation. On the other hand, they contribute to essential trophic functions such as neural patterning, bone morphogenesis and ductal branching in mammary glands. Thus, macrophages are extremely versatile cells that can respond efficiently to tissue micro environmental cues by polarizing to distinct phenotypes, depending on the functions they need to perform. Indeed, functional diversity and plasticity are hallmarks of these cells.

Macrophages may also play a detrimental role. An overwhelming body of literature has indicated their crucial role in pathogenesis. The list includes sepsis, cancer, metabolic syndrome, immunodeficiency, auto-immune disease-virtually impacting every major pathology that we know. These observations have suggested macrophages and their related molecules as potential targets in therapeutic applications. Available evidence proclaims macrophages as a key player in homeostasis, host defense and disease. Crucial developments in the past few years call for a re-evaluation and update of our understanding of macrophages. The present book is an endeavour that attempts provide state-of-the art knowledge of these cells in health and disease.

Insight into the role of hormones, particularly estrogen and testosterone, in health and disease etiology – including interactions with other hormone pathways – has dramatically changed. Estrogen and androgen receptors, with their polymorphisms, are key molecules in all tissues and are involved in a number of homeostatic mechanisms but also pathological processes including carcinogenesis and the development of metabolic and neurological disorders such as diabetes and Alzheimer’s disease. Endocrine disrupting chemicals (EDCs) can interfere with the endocrine (hormone) systems at certain dosages and play a key role in the pathology of disease. Most known EDCs are manmade and are therefore an increasing concern given the number commonly found in household products and the environment. This book will cover the mechanisms of EDC pathology across the spectrum of disease, as well as risk assessment and government and legal regulation to provide a holistic view of the current issues and cutting-edge research in the topic. With contributions from global leaders in the field, this book will be an ideal reference for toxicologists, endocrinologists and researchers interested in developmental biology, regulatory toxicology and the interface between environment and human health.

Insight into the role of hormones, particularly estrogen and testosterone, in health and disease etiology – including interactions with other hormone pathways – has dramatically changed. Estrogen and androgen receptors, with their polymorphisms, are key molecules in all tissues and are involved in a number of homeostatic mechanisms but also pathological processes including carcinogenesis and the development of metabolic and neurological disorders such as diabetes and Alzheimer’s disease. Endocrine disrupting chemicals (EDCs) can interfere with the endocrine (hormone) systems at certain dosages and play a key role in the pathology of disease. Most known EDCs are manmade and are therefore an increasing concern given the number commonly found in household products and the environment. This book will cover the mechanisms of EDC pathology across the spectrum of disease, as well as risk assessment and government and legal regulation to provide a holistic view of the current issues and cutting-edge research in the topic. With contributions from global leaders in the field, this book will be an ideal reference for toxicologists, endocrinologists and researchers interested in developmental biology, regulatory toxicology and the interface between environment and human health.

In September 2005 an International Meeting on “Targeted Therapies in Cancer: Myth or Reality” was held in Milan. This successful Meeting was intended to represent a forum for scientists and clinicians working in cancer drug discovery and therapy to share their reflections and experiences on how the paradigm shift from empiricism to molecular targeted therapies is contributing to the translation of basic knowledge into new therapies for cancer patients. This book collects the contributions given by scientists and clinicians, from Academia and Industry, who participated to this Meeting.

We hope that this book contributes to improve our approach to cancer drug discovery and, ultimately, to find new, more efficacious and better tolerated drugs for cancer patients. It provides an overview of diverse approaches ranging from drug discovery to cellular therapy. Although this change in paradigm has been useful, its entry into the clinical arena was associates with unforeseen problems including the emergence of resistance, unexpected side effects and failures. Time is therefore ripe for a critical cultural reflection on the state of the art, prospects and limitations. Ultimately, is targeted therapy in cancer a myth or a reality?

Macrophages are a key component of the innate immune system and play an integral role in host defense and homeostasis. On one hand, these cells contribute to host defence by triggering inflammation, displaying microbicidal/tumoricidal properties, regulating the activation of adaptive immunity and promoting resolution of inflammation. On the other hand, they contribute to essential trophic functions such as neural patterning, bone morphogenesis and ductal branching in mammary glands. Thus, macrophages are extremely versatile cells that can respond efficiently to tissue micro environmental cues by polarizing to distinct phenotypes, depending on the functions they need to perform. Indeed, functional diversity and plasticity are hallmarks of these cells.

Macrophages may also play a detrimental role. An overwhelming body of literature has indicated their crucial role in pathogenesis. The list includes sepsis, cancer, metabolic syndrome, immunodeficiency, auto-immune disease-virtually impacting every major pathology that we know. These observations have suggested macrophages and their related molecules as potential targets in therapeutic applications. Available evidence proclaims macrophages as a key player in homeostasis, host defense and disease. Crucial developments in the past few years call for a re-evaluation and update of our understanding of macrophages. The present book is an endeavour that attempts provide state-of-the art knowledge of these cells in health and disease.

Insight into the role of hormones, particularly estrogen and testosterone, in health and disease etiology – including interactions with other hormone pathways – has dramatically changed. Estrogen and androgen receptors, with their polymorphisms, are key molecules in all tissues and are involved in a number of homeostatic mechanisms but also pathological processes including carcinogenesis and the development of metabolic and neurological disorders such as diabetes and Alzheimer’s disease. Endocrine disrupting chemicals (EDCs) can interfere with the endocrine (hormone) systems at certain dosages and play a key role in the pathology of disease. Most known EDCs are manmade and are therefore an increasing concern given the number commonly found in household products and the environment. This book will cover the mechanisms of EDC pathology across the spectrum of disease, as well as risk assessment and government and legal regulation to provide a holistic view of the current issues and cutting-edge research in the topic. With contributions from global leaders in the field, this book will be an ideal reference for toxicologists, endocrinologists and researchers interested in developmental biology, regulatory toxicology and the interface between environment and human health.

Insight into the role of hormones, particularly estrogen and testosterone, in health and disease etiology – including interactions with other hormone pathways – has dramatically changed. Estrogen and androgen receptors, with their polymorphisms, are key molecules in all tissues and are involved in a number of homeostatic mechanisms but also pathological processes including carcinogenesis and the development of metabolic and neurological disorders such as diabetes and Alzheimer’s disease. Endocrine disrupting chemicals (EDCs) can interfere with the endocrine (hormone) systems at certain dosages and play a key role in the pathology of disease. Most known EDCs are manmade and are therefore an increasing concern given the number commonly found in household products and the environment. This book will cover the mechanisms of EDC pathology across the spectrum of disease, as well as risk assessment and government and legal regulation to provide a holistic view of the current issues and cutting-edge research in the topic. With contributions from global leaders in the field, this book will be an ideal reference for toxicologists, endocrinologists and researchers interested in developmental biology, regulatory toxicology and the interface between environment and human health.