Every year in the United States, 160,000 cases of colorectal cancer are diagnosed, and 57,000 patients die of the disease, making it the second leading cause of death from cancer among adults.1 The disease begins as a benign adenomatous polyp, which develops into an advanced adenoma with high-grade dysplasia and then progresses to an invasive cancer.2 Invasive cancers that are confined within the wall of the colon (tumor–node–metastasis stages I and II) are curable, but if untreated, they spread to regional lymph nodes (stage III) and then metastasize to distant sites (stage IV).3-5 Stage I and II tumors are curable by surgical excision, and up to 73% of cases of stage III disease are curable by surgery combined with adjuvant chemotherapy.3,4,6 Recent advances in chemotherapy have improved survival, but stage IV disease is usually incurable.3,4
The clinical behavior of a colorectal cancer results from interactions at many levels (Fig. 1). The challenges are to understand the molecular basis of individual susceptibility to colorectal cancer and to determine factors that initiate the development of the tumor, drive its progression, and determine its responsiveness or resistance to antitumor agents. This review summarizes areas of current knowledge, recognizing that the topics presented are only fragments of the total picture.