The introduction of new anticancer drugs and drug combinations, as well as the use of high-dose chemotherapy with growth factor and hemopoietic stem cell support, has greatly increased clinical remission rates. Unfortunately palliation, rather than cure, remains the most realistic goal of chemotherapy for many patients. The failure to cure metastatic cancer is commonly attributed to drug "resistance." Resistance can be broadly viewed as the survival of malignant cells because of a failure to deliver an effective drug dose to the (cellular) target, resulting from any one of or combination of individual factors. For example, inter-individual genetic differences in drug metabolism, as well as differences in tumor kinetics and vascularization, may be important for treatment outcome. In addition, numerous molecular mechanisms of resistance have been elucidated at the level of the individual tumor cell.
The present volume reviews clinically relevant aspects of the pharmacokinetics of commonly used anticancer agents as well as mechanisms of cellular/experimental resistance to such agents. This extends to technological advances that enable high-throughput studies of genetic polymorphisms, which has opened up new avenues to the study of drug resistance and to the individualization of chemotherapy in order to decrease clinical toxicity and optimize treatment results.
"This text provides a comprehensive review of the mechanisms of resistance to cancer chemotherapuetic agents. Leading experts discuss molecular and biochemical pathways that influence cytotoxicity. Knowledge of these potential obstacles to therapy will allow for the development of more effective strategies to treat malignantdiseases."
Steven T. Rosen, M.D., Series Editor

Over the last several decades, the introduction of new chemotherapeutic drugs and drug combinations has resulted in increased long term remission rates in several important tumor types. These include childhood leukemia, adult leukemias and lymphomas, as well as testicular and trophoblastic tumors. The addition of high-dose chemotherapy with growth factor and hemopoietic stem cell support has increased clinical remission rates even further. For the majority of patients with some of the more common malignancies, however, palliation (rather than cure) is still the most realistic goal of chemotherapy for metastatic disease. The failure of chemotherapy to cure metastatic cancer is commonly referred to among clinicians as "drug resistance". This phenomenon can, however, often be viewed as the survival of malignant cells that resulted from a failure to deliver an effective drug dose to the (cellular) target because of anyone of or combination of a multitude of individual factors. Clinically, this treatment failure is often viewed as the rapid occurrence of resistance at the single cell level. However, in experimental systems, stable drug resistance is usually relatively slow to emerge.