Many colorectal cancers are likely to have spread from the site where they first formed to other parts of the body long before the original tumor can be detected by current screening tests, new study results suggest. Most cancer researchers have assumed that the spread, or metastasis, of tumors typically occurs later in the disease process. The general idea has been that as tumors grow and cancer cells accumulate more and more genetic changes, or mutations, some cells acquire the ability to move from the primary tumor into the bloodstream or lymphatic system, to migrate to a distant location in the body, and to grow into tumors in the new location. But that’s not what Christina Curtis, Ph.D., of Stanford University School of Medicine, and her team found. Rather, their genomic analysis of both original, or primary, colorectal tumors and metastatic tumors from the same patients, coupled with computer simulations, led them to conclude that colorectal cancer can spread very soon after the original tumor has developed—and maybe years before the disease is diagnosed. Their findings, published June 17 in Nature Genetics, open a window for very early detection of metastatic colorectal cancer and could eventually help doctors identify those patients who need more aggressive systemic treatments, such as chemotherapy given after surgical removal of the tumor, Dr. Curtis said. Treatments that specifically target metastatic tumors do not yet exist, said Nancy Boudreau, Ph.D., chief of the Tumor Metastasis Branch in NCI’s Division of Cancer Biology. Metastatic cancer is notoriously challenging to treat, and metastasis accounts for most cancer-related deaths. The NCI-funded study is significant, Dr. Boudreau said, because “it shows, for the first time in patients, that some tumor cells are capable of metastasizing from the get-go.” And the new findings may provide clues on how to target and eliminate such cells in the bloodstream, she said.