'Light' from low level laser therapy, through a process called photobiomodulation (PBM), has been in existence in supportive care in cancer, in particular in the management of oral mucositis (OM) in patients undergoing chemotherapy, radiation therapy and haematopoietic stem cell transplantation. In this book the authors attempt to portray the current status of the supportive care interventions that are possible with PBM using low level laser therapy (LLLT) in patients undergoing cancer treatment for solid tumours, harmatological malignancies, and head and neck cancers.

The discovery of the anti-tumour activity of cisplatin in 1965, and its subsequent introduction into clinical trials in 1971, was the catalyst for a major research effort into the potential of metal compounds in cancer therapy. This book provides a discussion of metal compounds in cancer therapy. This book should be of interest to research workers in the pharmaceutical industry, particularly tumour pharmacologists, tumour biologists, medicinal chemists and oncologists.

This book will be a guide to understanding resistance against targeted therapeutic approaches for cancer using immunotoxins. It contains a detailed review of the history and development of targeted therapy. As well, it includes an in-depth description of the molecular and cellular mechanisms involved in cancer resistance and several novel methods to overcome resistance. Each chapter discusses different aspects of resistance and covers all the factors that may contribute to resistance in cancer cells. Finally, this volume highlights the recent findings and advances associated with tackling cancer resistance.

One of the most important developments in the field of cardiovascular medicine over the last two decades has been recognition of the key role played by arterial thrombosis in the pathogenesis of acute coronary syndromes, ischemic complications of percutane- ous coronary revascularization, and coronary and peripheral atherosclerosis. The phar- macologic armamentarium directed against vascular thrombosis has thus expanded substantially during that time, with development of new fibrinolytic agents, low-molecu- lar-weight heparins, direct thrombin inhibitors, antagonists to platelet activation, and the platelet glycoprotein lIb/IlIa inhibitors. Though clinical investigations of these com- pounds have been marked by failures as well as successes, there is little doubt that enhanced antithrombotic therapies have markedly improved the outcome of patients undergoing coronary revascularization or with acute coronary syndromes. Glycoprotein IIblIlIa receptor antagonists were introduced into clinical practice to overcome the limitations of approaches that inhibit only individual pathways of platelet activation. Multiple mechanisms of platelet activation in response to different agonists converge on the platelet membrane glycoprotein IIblIlIa complex, the "final common pathway" of platelet aggregation. The clinical hemorrhagic syndrome caused by a rare inherited defect in this receptor (Glanzmann' s thrombasthenia), characterized by muco- cutaneous and postsurgical bleeding, but infrequent spontaneous organ (particularly central nervous system) bleeding, suggested that therapeutic inhibition of this receptor might be a potent, yet well-tolerated means of treating thrombotic disorders.

Antifolates are an important class of anticancer drugs originally developed as anti leu- kemic agents, but now used, usually in combination with other drugs, for the treatment of a wide range of tumors, notably carcinomas of the head and neck, breast, germ cell tumors, non-Hodgkin's lymphoma, acute lymphoblastic leukemia, and osteogenic sar- comas. 5-Fluorouracil and its prodrugs also target, in part, the folate-dependent enzyme, thymidylate synthase. Furthermore, folate supplementation in the form of leucovorin, modulates 5-fluororuacil activity. 5-Fluorouracil is widely used in the treatment of colorectal and gastric cancer and in combination for other solid tumors such as breast and head and neck cancers. Ongoing clinical trials with the newer antifolates suggest that the range of solid tumors where these agents will be of use may broaden further. Half a century ago, interesting scientific and clinical discoveries suggested that folie acid was a vitamin involved in vital cellular metabolic processes. The folate analogs, aminopterin and methotrexate, were synthesized by the American Cyanamid Company in an attempt to interfere with these processes and were shown to have anticancer activity by Farber and his colleagues. Hence, the principle of antimetabolite therapy for the treatment of cancer was established. Biomedical research over the following years led to a deeper understanding of the complex biochemical pharmacology of folates and antifolates. Selective antimicrobial agents were discovered, but more tumor-selective anticancer agents did not immediately emerge.

Antibody-directed enzyme prodrug therapy (ADEPT) directly addresses the major problem in cancer chemotherapy-its lack of selectivity. Antibody delivery combined with the amplification provided by the enzymatic activation of prodrugs enables selection to be made between tumour and normal tissue. ADEPT offers a novel field of opportunities in the therapy of systemic cancer and may be a major advance for the treatment of solid tumours. This book is the first to describe ADEPT in detail. Each chapter reviews an aspect of the immunology, enzymology, biochemistry, chemistry, and cancer chemotherapy which have been integrated into the ADEPT concept. An additional chapter describes the related approach of gene-directed enzyme prodrug therapy (GDEPT). This latter approach is still in its infancy but ADEPT has entered the clinic. The initial clinical studies with ADEPT are included and discussed in detail.

Biological inorganic chemistry is a field of research at the interface of inorganic and biological chemistry. The rapidly developing insights into the role of metals in biological systems has far-reaching implications not only for biological science but also for related disciplines, ranging from molecular medicine to the environment. In each volume the reader, whether engaged in chemistry, biochemistry, biology or molecular medicine, receives a comprehensive summary and critical overview of a topic of high current interest written by leading international experts.

In 1971, J. Folkman published in the New England Journal of Medicine a hypothesis that tumor growth is angiogenesis-dependent. Folkman introduced the concept that tumors probably secrete diffusible molecules that could stimulate the growth of new blood vessels toward the tumor and that the resulting tumor neovascularization could conceivably be prevented or interrupted by angiogenesis inhibitors. Solid and haematological tumors consist of an avascular and a subsequent vascular phase. Assuming that this depends on the release of angiogenic factors, acquisition of angiogenic capability can be seen as an expression of progression from neoplastic transformation to tumor growth and metastasis.

Beginning in the 1980 s, the biopharmaceutical industry began exploiting the field of antiangiogenesis for creating new therapeutic compounds for modulating new blood vessels in tumor growth. In 2004, Avastin (Bevacizumab), a humanized anti-VEGF monoclonal antibody, was the first angiogenesis inhibitor approved by the Food and Drug Administration for the treatment of colorectal cancer. At present, it has been estimated that over 20,000 cancer patients worldwide have received experimental form of antiangiogenic therapy.

This book offers a historical account of the relevant literature. It also emphasizes the crucial and paradigmatic role of angiogenesis as a biological process and the significance of antiangiogenic approach for the treatment of tumors."

The 7th International Symposium on Platinum and other metal coordination compounds in Cancer Chemotherapy, ISPCC '95, organized by the European Cancer Centre, was held in Amsterdam, the Netherlands, March 1-4, 1995. As with previous ISPCC meetings, the goal of ISPCC '95 was to bring together c1inicians, clinical investigators, scientists, and laboratory workers from many disciplines to promote further collaboration and cooperation in the development of new platinum and other metal coordination compounds as weil as in new ways to use 'c1assical' drugs as cisplatin and carboplatin in the treatment of cancer. Important aspects addressed by experts in the field inc1uded the synthesis and activity of new platinum compounds, the biochemistry and molecular pharrnacology as weil as the c1inical pharrnacology of this c1ass of antineoplastic agents, an overview of current c1inical studies, one special minisymposium on the mechanisms of cell kill of platinum, and one on resistance against platinum compounds. Finally, the current status of development of nonplatinum metal complexes was discussed. This volume contains the contributions of the various speakers at ISPCC '95 and provides an up-to-date and comprehensive overview of this important c1ass of anticancer agents, ranging from synthesis and molecular pharrnacology on one hand to c1inical pharrnacology and cIinical investigations on the other hand. The Organizing Corrunittee and Editors wish to express their gratitude to the contributors to this volume, to the various organizations and pharrnaceutical companies for their generous sponsoring of ISPCC '95, and to the Plenum Publishing Company for their help in producing this volume.

The last decade has seen a renaissance of the concept of individualized chemotherapy in oncology, markedly stimulated by the development of new in vitro chemosensitivity assays. The clinical utility of drug response assays has been evaluated in clinical trials and the results suggest that assay-assisted therapy selection may improve survival as well as economic outcomes. This volume comprises the proceedings of the first Symposium of the International Society for Chemosensitivity Testing in Oncology, ISCO-1, held in Homburg/Saar, Germany, in September 2001. The topics include: new in vitro drug-testing methods, tumor chemosensitivity assays, and the clinical relevance of assay-directed therapy.

Antibody-drug conjugates (ADCs) represent a promising therapeutic approach for cancer patients by combining the antigen-targeting specificity of monoclonal antibodies (mAbs) with the cytotoxic potency of chemotherapeutic drugs. In Antibody-Drug Conjugates, expert researchers provide detailed protocols for many of the key ADC techniques necessary for working in the field. These chapters and methodologies are aimed at the key tasks necessary to identify a suitable target, properly design the mAb, the linker and the payload, as well as to conjugate them in a reproducible and scalable fashion. Written in the highly successful Methods in Molecular Biology (TM) format, these detailed chapters include the kind of practical implementation advice that guarantees quality results. Authoritative and timely, Antibody-Drug Conjugates aims to further drive ADC development and thus help toward improving cancer treatments of the future.

Philip Rosenthal, MD, and a panel of leading malaria experts drawn from academia, the military, and international health organizations survey the latest scientific understanding of antimalarial chemotherapy, emphasizing the molecular mechanisms of resistance and the description of important new targets. Their survey covers the current status of malarial and antimalarial chemotherapy, the relevant biology and biochemistry of malaria parasites, the antimalarial drugs currently available, new chemical approaches to chemotherapy, and possible new targets for chemotherapy. Comprehensive and cutting-edge, Antimalarial Chemotherapy: Mechanisms of Action, Resistance, and New Directions in Drug Discovery clearly delineates all the basic and clinical research now addressing one of the world's major unresolved disease problems, work that is now powerfully driving the rapid pace of antimalarial drug discovery today.

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.

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.

This interdisciplinary volume collates research work on kinesins and cancer. Authors attempt to validate members of the kinesin superfamily as potential targets for drug development in cancer chemotherapy. The work begins by highlighting the importance of kinesins, summarising current knowledge and how they are shown to be crucial for mitosis. Chapters go on to explore how this family of proteins are emerging as a novel target for chemotherapeutic intervention and drug development. Readers will learn how kinesins travel along microtubules to fulfill their many roles in intracellular transport or cell division. Several compounds that inhibit two mitotic kinesins (called Eg5 and CENP-E) have entered Phase I and II clinical trials and are explored in these chapters. Additional mitotic kinesins are currently being validated as drug targets, raising the possibility that the repertoire of kinesin-based drug targets may expand in the future. The book is suitable as a reference standard for the field of kinesins and cancer. It will interest those in academia and pharmaceutical companies, and anyone with an interest in the medical relevance of these proteins, which cutting edge methodologies are now enabling us to understand in astonishing detail.

Great advances were made in the pharmacologic-based treatment of cancer in prior decades. However, despite a marked increase in our understanding ofcell and molecular mechanisms underlying the neoplastic process, therapy for advanced disease remains limited. While the reasons for this are many, it is generally accepted that advanced neoplasms contain a relatively large number of genetic and molecularalterations contributingto the maintenanceofthe neoplastic process. Such a situation precludes easy pharmacologic intervention. However, our ability to detect cancer at an earlier stage, coupled with our increased understandingofcarcinogenesis, are propellingboth basic and clinical scientiststo pursue early intervention/chemopreventive approaches. This is based upon the notion that fewer molecularaberrations are presentearlyon inthedisease process. It also takes advantage ofthe fact that advances in both technology, and in the field ofcancer biology, coupled with a heightened vigilance, have increased our ability to detect early disease more readily. The chemopreventive approach is highly attractive for a number ofreasons. First, treatment ofpre-neoplastic, or early neoplastic, lesions would prevent the significant mobility and mortality associated with advanced neoplastic disorders.

The title of this monograph, Brain Tumor Research and Therapy, is the name of the Conference itself, which had its inaugural meeting in the United States in 1975 andhas since progressed to the international scale. In Japan, the first conference ofits kind was organized by Dr. Takao Hoshino and me and was held at Nikko in 1980, hence its name, the Nikko Conference on Brain Tumor Research and Therapy. Though it started as a small, closed meeting, the conference has grown considerably, and in 1992 it was reorganized as the Japanese Conference on Brain Tumor Research and Therapy and was opened to all neurosurgeons and neuropathologists interested in the study of brain tumor problems and who are participating in this field. The main purpose of the Conference on Brain Tumor Research and Therapy is the candid and informed discussion of the most up-to-date developments in basic re search and clinical treatment of brain tumors. The 3rd Japanese Conference on Brain Tumor Research and Therapy was held at Nasu (Tochigi Prefecture), Japan, in No vember 1994. It was a great honor to welcome many distinguished guests from over seas who kindly attended each session and made valuable contributions.

This book presents a comprehensive collection of essential and up-to-date methods for studying both the biology of microtubules and the mechanisms of action of microtubule-interacting drugs. The book contains a straightforward presentation of readily reproducible protocols, tips for troubleshooting, and advice on avoiding common mistakes. Basic scientists and clinical researchers will benefit from this collection.

Cancer drug discovery has been and continues to be a process of ingenuity, serendip ity, and dogged determination. In an effort to develop and discover better therapies against cancer, investigators all over the world have increased our knowledge of cell biology, biochemistry, and molecular biology. The goal has been to define therapeuti cally exploitable differences between normal and malignant cells. The result has been an increased understanding of cellular and whole-organism biology and an increased respect for the flexibility and resiliency ofbiologically systems. Thus, as some new therapeutic targets have been defined and new therapeutic strategies have been attempted, so have some new biological hurdles resulting from tumor evasion of the intended therapeutic attack been discovered. Historically, anticancer drugs have originated from all available chemical sources. Synthetic molecules from the chemical industry, especially dyestuffs and warfare agents, and natural products from plants, microbes, and fungi have all been potential sources of pharmaceuticals, including anticancer agents. There is no shortage of molecules; the challenge has been and continues to be methods of identifying molecules that have the potential to be therapeutically important in human malignant disease. "Screening" remains the most important and most controversial method in cancer drug discovery. In vitro screens have generally focused on cytotoxicity and have identified several highly cytotoxic molecules. Other endpoints available in vitro are inhibition of proliferation, 3 inhibition of [ H]thymidine incorporation into DNA and various viability assays, based most frequently on dye exclusion or metabolism.