During the last 20 years it has become increasingly clear that the tumor micro-environment, the tumor stroma with its cellular end extracellular components, plays an crucial role in regulating tumor growth and progression. This book on “Tumor-associated fibroblasts and their matrix” as part of the series on “Tumor-Microenvironment” is the first comprehensive discussion of these two main players of the tumor microenvironment. The best experts in this new area of tumor research and therapy review the role of these major components in the tumor stroma in the process of tumor development and progression. They discuss their interaction with other players such as blood vessels and immune cells, and show novel perspectives for tumor therapy. This compilation of excellent contributions of the best known experts in this important field in cancer research and therapy is a must for all scientists engaged in basic and clinical research. Increasing evidence of successful targeting of both cellular and matrix components in tumor therapy renders this book of particular interest for scientists engaged in pharmaceutical industry searching for new components for cancer therapy.

Genetic alterations in cancer, in addition to being the fundamental drivers of tumorigenesis, can give rise to a variety of metabolic adaptations that allow cancer cells to survive and proliferate in diverse tumor microenvironments. This metabolic flexibility is different from normal cellular metabolic processes and leads to heterogeneity in cancer metabolism within the same cancer type or even within the same tumor. In this book, we delve into the complexity and diversity of cancer metabolism, and highlight how understanding the heterogeneity of cancer metabolism is fundamental to the development of effective metabolism-based therapeutic strategies. Deciphering how cancer cells utilize various nutrient resources will enable clinicians and researchers to pair specific chemotherapeutic agents with patients who are most likely to respond with positive outcomes, allowing for more cost-effective and personalized cancer therapeutic strategies.

Abstract: Tumor associated macrophages (TAMs) perform various task that are essential for tumor growth, angiogenesis, metastasis, and tumor invasion. Growth factors, chemokines, cytokines and the extra cellular matrix in the tumor microenvironments signal the TAMs to perform these tasks. The tumor microenvironment is not homogeneous and can be classified into several distinct regions such as sites of tumor invasion, perivascular, hypoxic and stromal regions. Each of these sites likely has different cytokines and signaling molecules in their microenvironment that might signal and direct the function of TAMs. The purpose of this project is to isolate and analyze TAMs from distinct tumor regions to gain a better understanding of the mechanism behind the specialized role of these TAMs. As a first step towards this goal, micro array analysis was conducted on flow sorted TAMs and developmental macrophages expressing yellow fluorescence protein (YFP). Micro array data from age matched developmental macrophages was compared to TAMS from early, premalignant stage of breast cancer, and late stage metastatic breast cancer to find the genes which were upregulated in TAMs versus developmental macrophages, and in late stage TAMs versus TAMs from the earlier premalignant stage of breast cancer. From this list of genes upregulated in TAMs, candidate cell surface macrophage markers that could be used to classify TAMs based on there association with one of the distinct tumor microenvironments was selected. These candidate markers will be used to visualize macrophages associated with different regions within the tumor microenvironment using immuno-staining of tumor sections. In preliminary work, CD16 was selected as one potential candidate gene that was upregulated late in tumor development compared to earlier stages. Immunostaining indicated CD16 was expressed on a set of macrophages near blood vessels near the tumors, but not in macrophages located within tumors. Further evaluation of these markers would facilitate isolation of different subsets of macrophages within tumor and understanding the function of these macrophages in tumor microenvironment. Another major cell group involved in all the changes in the tumor microenvironment discussed is the fibroblast. Originally the fibroblast inhibits the growth of the tumor. However through natural selection tumors evolve to change the microenvironment and like wise the function the fibroblast are performing to aid in tumor progression rather than suppress tumor progression. These fibroblast reprogrammed by the tumor cells are called tumor associated fibroblast TAFs. TAFs aid in tumor progression by angiogenesis, immune suppression, and matrix remodeling, providing growth and anti apoptotic factors and aid in metastasis by recruiting TAMs. A key gene involved with this is IKK. It is our hypothesis that ablating IKK in the fibroblast will lead to a reduction of tumor growth.

This volume presents the entire breadth of translational cancer research and brings together members of academia and industry in the expectation of accelerating interactions and progress in the field. A variety of key topics are presented, beginning with discovery of molecular targets and pathways (oncogene, cell survival, tumor suppression, cell death), host-neoplasm interactions (cell adhesion, matrix proteases), early detection, monitoring progression, understanding tumor progression and metastasis, immune surveillance, in vivo molecular imaging, animal models, drug discovery including chemistry, high-throughput assays, mechanism determination, target validation, therapeutic window and some progress in clinical trials for more advanced agents and targets.

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.

Today, the arsenal of “high-precision” or “targeted” radiotherapy includes a variety of techniques and approaches that, like the pieces of a puzzle, need to be put together to provide the prostate cancer patient with high-level optimized radiation treatment. This book examines in detail the role of these innovative radiation techniques in the management of prostate cancer. In addition, a variety of current controversies regarding treatment are carefully explored, including whether prophylactic treatment of the pelvic lymphatics is essential, the magnitude of the effect of dose escalation, whether a benefit accrues from hypofractionation, and what evidence exists for the superiority of protons or heavy ions. Radiotherapy in Prostate Cancer: Innovative Techniques and Current Controversies is intended for both radiation oncologists and urologists with an interest in the up-to-date capabilities of modern radiation oncology for the treatment of prostate cancer.

Holland-Frei Cancer Medicine, Ninth Edition, offers a balanced view of the most current knowledge of cancer science and clinical oncology practice. This all-new edition is the consummate reference source for medical oncologists, radiation oncologists, internists, surgical oncologists, and others who treat cancer patients. A translational perspective throughout, integrating cancer biology with cancer management providing an in depth understanding of the disease An emphasis on multidisciplinary, research-driven patient care to improve outcomes and optimal use of all appropriate therapies Cutting-edge coverage of personalized cancer care, including molecular diagnostics and therapeutics Concise, readable, clinically relevant text with algorithms, guidelines and insight into the use of both conventional and novel drugs Includes free access to the Wiley Digital Edition providing search across the book, the full reference list with web links, illustrations and photographs, and post-publication updates