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Cellular drug resistance is a major limitation to the success of chemotherapy of leu kemia and lymphoma. The importance of this has now been recognized by both clinicians and scientists. It is of utmost importance to bridge the gap between laboratory and clinic in this field of research. This is the main purpose of the series of International Symposia on Drug Resistance in Leukemia and Lymphoma. These are held every three years in Am sterdam, The Netherlands, since 1992. This book contains the proceedings of the third of these meetings, organised in 1998. The book covers all important aspects of drug resistance in leukemia and lymphoma, both in the form of extensive reviews as in manuscripts describing original data. General mechanisms of resistance are discussed, including the drug resistance related proteins p glycoprotein, MRP (multi-drug resistance protein) and LRP (lung resistance protein), and the role of glutathione and glutathione-S-transferases. Moreover, more drug type-specific mechanisms of resistance are a topic, such as for glucocorticoids and antifolates. Much in formation is provided on apoptosis and its regulators, and on the results of cell culture drug resistance assays. Several papers focus on the modulation or circumvention of drug resistance.
The last ten years have seen the publication of a vast amount of data regarding cellular resistance to drugs in cancer cells. Recent studies have demonstrated that drug resistance assays appear to be predictive of clinical response and suggest that clinicians should now be considering the potential applications of these assays in the treatment of patients with hematological neoplasms. This collection of papers from the International Symposium on the Clinical Value of Drug Resistance Assays in Leukemia and Lymphoma, Amsterdam, 1992, provides a state-of-the-art discussion on drug resistance assays and their role in the design and individualization of treatment protocols.
Drug Resistance in Leukemia and Lymphoma contains material presented at the 2nd International Symposium in Drug Resistance in Leukemia and Lymphoma held at the Free University in Amsterdam in March 1995. In the last decade many studies have been performed in the field of drug resistance. This book reviews the current status and indicates future directions of such studies. Both laboratory scientists and clinicians have recognized the importance of drug resistance for the clinical outcome of patients with leukemia and lymphoma. New in vitro cell culture assays have been developed and the in vitro drug resistance measured with these assays has been shown to correlate with both short and long-term clinical response to chemotherapy. This book is, therefore, an essential guide for researchers and clinicians.
Over the past few decades, lymphoma patient outcomes have improved as a result of multidrug chemotherapy and radiation therapy, intensification of treatment, improvement in supportive care, and better imaging and staging systems. Even more recently, there has been tremendous progress in the understanding of cancer cell biology and its microenvironment which has resulted in the development of biologic agents, also called "target" therapies. These therapies are more specific in targeting cancer cells either directly or via enhancement of the immune system. Many clinical studies have focused on biological agents in combination with traditional chemotherapy with the goal of improved outcomes, or reduced acute long term complications that are associated with lymphoma therapy. This volume will review different classes of "target" drugs that have been developed, approved, or are under investigation in the field of lymphoma therapy. The discussion will not only be on the understanding of the mechanisms of action or clinical response of those agents, but will also help the reader to understand the nature of lymphoma biology in patients who relapse or are refractor after exposure to those drugs. Contributors will discuss what is currently known about mechanisms of tumor-related or host-related resistance, and how to overcome this resistance. This understanding is crucial given the dismal outcomes of patients with relapsed or refractory lymphomas. The book provides a unique opportunity to review and reflect on the recent successes and pitfalls of the modern lymphoma therapy era.
A major objective of this book is to reveal unprecedented opportunities to understand and overcome drug resistance through the clinical assessment of rational therapeutic drug combinations and the use of predictive and prognostic biomarkers to enable patient stratification and tailor treatments. It offers to the readers an updated overview on the possible reasons of failure of new and promising therapeutic opportunities.
International authorities review the mechanisms and clinical implications of drug resistance in cancer.