Metastasis in colorectal cancer: what makes the tumor aggressive?

While local control of colorectal cancer can usually be obtained, distant spread is frequent and nearly always results in incurable disease and death. Therefore, the critical determinant of aggressiveness of colorectal cancers is the ability to disseminate widely. While the molecular biology of colorectal carcinogenesis is comparatively well understood, the mechanisms important in metastasis remain relatively cryptic. Conceptually, metastasis is a multistep process with a number of potential therapeutic targets. Critical steps include angiogenesis, local invasion, embolization to distant sites, and extravasation. Identification of high risk tumors may allow more judicious use of effective, but nonselective, cytotoxic adjuvant therapy. Specific inhibitors of particular steps of metastasis are already in various stages of testing.