ABSTRACT

Colorectal cancer is a major cause of cancer-related death in the United States and other industrialized countries (1,2). This unfortunate fact is due in part to the marked resistance of colon cancer cells to available therapeutic agents (Table 1) (2,3). In fact, the sole truly effective therapy available for colorectal cancer at present is surgical intervention. Thus, there is no truly effective therapy available to manage metastatic colorectal cancer. Neither chemotherapeutic drugs nor biological response modifiers (e.g., interferons) have achieved major improvements in the survival of colon cancer patients (2). The inherent resistance of colon cancer to chemotherapeutic agents is termed intrinsic drug resistance. In contrast, acquired drug resistance is commonly observed in cancers that initially respond to chemotherapy (e.g., breast cancer). Acquired drug resistance is defined as resistance that develops as a result of exposure of cancer cells to chemotherapy ( 4,5).