Clinical Cancer Treatment and Drug Resistance: The Interface of the Clinic and the Laboratory

Abstract

The development of drug resistance is a major roadblock to successful systemic cancer therapy. Although much research has been devoted to this subject in recent years, these efforts have been focused primarily on the molecular mechanisms operative in resistance to chemotherapy. Older, traditional approaches to drug resistance developed from a knowledge of clinical factors such as “sanctuary sites” of metastatic disease and stemmed from empirical observations relating tumor bulk to the likelihood of successful therapy. These observations led to the use of intrathecal chemotherapy for diseases metastatic to the central nervous system, to experimentation with intraperitoneal chemotherapy, and to several theories relating tumor size to chemotherapeutic efficacy. Little attention has been given to the interplay of molecular factors and clinical factors in the development of drug resistance in patients receiving systemic cancer treatment. In this volume we seek to give an overview of known molecular and clinical factors which may result in cancer drug resistance and the probable interplay of these factors in the evolution of resistance in man. Finally, we discuss treatment approaches that hold promise for overcoming the hurdles that exist between current technological possibilities and practical aspects of achieving cancer cure.