EARLY MTSTATIC SPREADING OF SOME CELLS

Metastases are generally thought of as a later event that occurs some time after the primary cancer develops, but new research shows that metastases may be seeded years before cancer is even diagnosed by clones that were "born to be bad." This tantalizing idea has experimental support, at least for colorectal cancer, from research conducted by Christina Curtis, PhD, and her lab at the Stanford University School of Medicine in California.
The team showed that metastatic 'seeding' (ie, when the first tumor cell colonizes the metastatic site) is a very early event and likely happens years before the primary cancer is even detected.
"In 80% of patients with metastatic CRC, we determined that seeding of the metastatic sites occurred exceedingly early, before the primary tumor was clinically detectable," Curtis told Medscape Medical News.
"Our data suggest that some clones are born to be bad, with their malignant and potentially metastatic potential specified early," she added.
The study was published online June 17 in Nature Genetics.
The Curtis lab is now in the process of determining if the paradigm of early metastatic seeding is also true of other cancers, including those of the breast and lung.

Implications for the Clinical Translation

Approached for comments about this new research, pathologist Anirban Maitra, MBBS, of the University of Texas MD Anderson Cancer Center in Houston, pointed out that metastases are the most common cause of cancer death in solid cancers.
"What this study is telling us is that metastases observed from an image on a CT scan is an imprint of what was seeded years ago, and profiling a primary tumor provides an opportunity to address metastases before they are actually detected," he told Medscape Medical News.
These observations are of immediate clinical relevance. Dr Anirban Maitra
"These observations are of immediate clinical relevance and the findings provide the opportunity to predict the biology of CRC tumors on the basis of genomic profiling of the primary tumor," said Maitra, who was not involved with the current study.
Profiling primary tumors before obvious metastatic spread has occurred offers an opportunity to identify which tumors are indolent and which are aggressive, he explained. "Because metastases might be predicted based on the profiling of the primary tumor, therapy can be appropriately tailored so that patients with indolent tumors are not overtreated and those with tumors 'born to be bad' can be treated aggressively from early on," he said.

Findings Upend Long-Held Dogma About Metastasis

For Curtis, who runs a cancer computational and systems biology lab at Stanford and codirects the Molecular Tumor Board, the journey to trace a tumor's evolution started several years ago. In a study published in 2015, Curtis challenged the prevailing notion of ongoing sequential clonal evolution. Her lab proposed a "Big Bang" model of colorectal tumor growth.
According to this model, after the tumor is founded, it evolves in an effectively neutral fashion such that additional mutations are largely passenger events and do not result in subsequent clonal expansions. "These findings also provided the first quantitative evidence for the early origin of intra-tumor heterogeneity," she told