Clinically Relevant Resistance in Cancer Chemotherapy

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 tumour 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 tumour cell. This 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.