So, one knows, let’s say in the case of breast cancer, that there are many thousands, even millions of cells that disseminate to distant sites in the body and remain there - thousands of them, after the primary tumor is removed or eliminated by chemotherapy and a woman who’s had a primary breast cancer, she may develop metastases, five, ten or twenty years later. What’s happened in the interim? Clearly the metastatic cells were unapparent, one could not even not really detect their existence. After all, imagine that we have in our body thirty thousand billion cells, how could one ever find a small group of cells: ten, a hundred, even a thousand. But the question is: what triggers the eruption of these previously silent, these previously dormant, these previously latent, disseminated cells? And I don’t know all of the answers - I don’t know many of the answers but we have two kind of interesting experiments that have been going on in my lab. In one case, we selected different cells that are non-metastatic and they’re seeded into the lung in the first four or five weeks. After they’re seeded in the lung, they don’t make metastases, and if you now induce inflammation in the lungs, now those cells will start to growing, they’re activated by the EMT program, actually. And they’ll form aggressive metastases. So, the surroundings of the cancer cells, the microenvironment, just like you said, turns out to be very important. The second story I would tell is work of the following sort: if you look at breast cancer patients who have undergone surgery for their primary tumors, within the first year after the surgery there’s a big peak of metastases which then goes down and they get small numbers of metastases for many years there after. What’s going on there? And our hypothesis was that this is surgery-induced activation of previously dormant metastases. So a post doc in my lab implanted tumors on one side of the mouse that are actually antigenic and therefore attract the attentions of the immune system, which usually on its own succeeds in eliminating these cancer cells; however, if on the other side of the mouse one creates a wound or a chronic wound, then now a lot of these otherwise eliminated tumors survive and grow out and form large tumors, simply because the wound healing response that starts at one side of the mouse suppresses the ability of the immune system to eliminate the cancerous cells that have been implanted on the other side of the mouse. So that’s another answer to your question, I don’t claim that these are going to be true for all kinds of suddenly apparent metastases, but they may contribute to our understanding of that mechanism.

Robert "Bob" Weinberg is Daniel K. Ludwig Professor for Cancer Research and director of the Ludwig Cancer Center at MIT, an American Cancer Society Research Professor, and is a founding member of the Whitehead Institute for Biomedical Research.

In 1982 he was one of the scientists to discover the first human oncogene, Ras, which causes normal cells to form tumors, and his lab also isolated the first known tumor suppressor gene, Rb.

He co-authored with Douglas Hanahan the landmark "Hallmarks of Cancer" paper in 2000, which laid out the six requirements for a healthy cell to become cancerous.