Signal Transduction In Cancer Metastasis

This book examines the signal mechanisms responsible for triggering a series of phenotypical changes of primary tumor which may lead to final colonization of the tumor in a second home. It highlights the initial stage of tumor metastasis.

One of the most exciting areas of cancer research now is the development of agents which can target signal transduction pathways that are activated inappropriately in malignant cells. The understanding of the molecular abnormalities which distinguish malignant cells from their normal counterparts has grown tremendously. This volume summarizes the current research on the role that signal transduction pathways play in the pathogenesis of cancer and how this knowledge may be used to develop the next generation of more effective and less toxic anticancer agents. Series Editor comments: "The biologic behavior of both normal and cancer cells is determined by critical signal transduction pathways. This text provides a comprehensive review of the field. Leading investigators discuss key molecules that may prove to be important diagnostic and/or therapeutic targets."

This work presents the most advanced discoveries from translational research laboratories directly involved in identifying molecules and signalling pathways that play an instrumental role in metastasis. In contrast to other works, conventionally focused on a single type of tumour, the various chapters in this book provide a broad perspective of the similarities and discrepancies among the dissemination of several solid malignancies. Through recurrent and overlapping references to molecular mechanisms and mediators, the readers will gain knowledge of the common ground in metastasis from a single source. Finally, an introductory chapter provides a clinical perspective of the problems presented by metastatic tumours for diagnosis and treatment. The work presented here is directed to researchers in tumour biology with a developing interest in metastatic dissemination as well as medical and graduate students seeking to expand and integrate the notions acquired in basic cancer biology and oncology courses.

International experts present innovative therapeutic strategies to treat cancer patients and prevent disease progression Extracellular Targeting of Cell Signaling in Cancer highlights innovative therapeutic strategies to treat cancer metastasis and prevent tumor progression. Currently, there are no drugs available to treat or prevent metastatic cancer other than non-selective, toxic chemotherapy. With contributions from an international panel of experts in the field, the book integrates diverse aspects of biochemistry, molecular biology, protein engineering, proteomics, cell biology, pharmacology, biophysics, structural biology, medicinal chemistry and drug development. A large class of proteins called kinases are enzymes required by cancer cells to grow, proliferate, and survive apoptosis (death) by the immune system. Two important kinases are MET and RON which are receptor tyrosine kinases (RTKs) that initiate cell signaling pathways outside the cell surface in response to extracellular ligands (growth factors.) Both kinases are oncogenes which are required by cancer cells to migrate away from the primary tumor, invade surrounding tissue and metastasize. MET and RON reside on both cancer cells and the support cells surrounding the tumor, called the microenvironment. MET and RON are activated by their particular ligands, the growth factors HGF and MSP, respectively. Blocking MET and RON kinase activation and downstream signaling is a promising therapeutic strategy for preventing tumor progression and metastasis. Written for cancer physicians and biologists as well as drug discovery and development teams in both industry and academia, this is the first book of its kind which explores novel approaches to inhibit MET and RON kinases other than traditional small molecule kinase inhibitors. These new strategies target key tumorigenic processes on the outside of the cell, such as growth factor activation by proteases. These unique strategies have promising potential as an improved alternative to kinase inhibitors, chemotherapy, or radiation treatment.

Metastasis of tumours is a sequence of events taking place after the appearance of a primary tumour. The potency of a tumour to metastasise greatly depends on the molecular interactions between tumour components (cellular differentiation and heterogeneity, surface antigenic determinants etc.) and the micro-environment. The complexity and diversity in the composition of tissue micro-environment is in great extent determining the metastatic behaviour or a primary tumour. Extracellular matrix composition, rearrangement of cytoskeleton, cell antigenicity , expression of metastasis-related novel genes, cell adhesion and novel therapeutical approaches such as blockage of angiogenesis, are the major topics discussed in detail in this volume.

Our limited understanding of cellular regulatory signal-transduction-networks has been a barrier to progress in improving the overall cure-rate of human cancers. Delineation of the physiologic roles of the specific regulatory signaling components, with known association with metastatic phenotypes, is a highly promising area which will likely provide the next generation of targeted strategies in the future of molecular cancer medicine. These signaling components are likely to be used in diagnosis, prognosis, and as novel targets for therapeutic development. This book brings together up-to-date summaries by leading cancer researchers on the major principles of cancer cell biology: survival, apoptosis, adhesion, and cell cycle deregulation. It is directed at clinicians and scientists working in the areas of experimental and molecular therapeutics, molecular medicine, translational cancer research, and bio-medical sciences in general.

Cancer is a multifaceted disease and overwhelmingly increasing experimental evidence has helped us to develop a deeper understanding of the role of signal transduction cascades in cancer development and progression. Tissue microarrays and next generation sequencing technologies have assisted us to gather missing pieces of jigsaw puzzle and we now know that deregulation of spatio-temporally controlled signaling cascades play fundamental role in metastasis and resistance against wide ranging therapeutics. This book offers a balanced overview of the rapidly emerging cutting edge research in molecular oncology and good source of knowledge for established oncologists, basic and medical students and pharmaceutical industry associated R&D departments.

about the involvement of signaling Transforming growth factor in tumor development and metastasis. plays a central role in the signaling network that controls morphogenesis, 2. THE BASICS OF growth and cell differentiation in SIGNALING multicellular organisms. The different members of this pleiotropic family of 2. 1. receptor signaling growth and differentiation factors seem to The family of growth factors regulate many processes in human disease consists of more than thirty members in and, in particular, tumor development. humans alone (15, 16). They cluster in Our understanding of how two major groups, the group composed of initiated signals are mediated has both the bone morphogenetic proteins increased dramatically in the last fifteen (BMP) and growth and differentiation years. Firstly, the prototype of factors (GDFs), and the group formed by this still constantly growing family, was the Activins, and Nodals. The two identified and cloned (1). Secondly, the groups differ in their use of receptors for family receptors were transmembrane receptors and the identified by expression cloning from subsequent activation of the mammalian tissue culture (2-7). Thirdly, transcriptional mediators (for recent genetic screens in Drosophila reviews see (13, 14, 17)).