Nicola Aceto is a cheerful person. When he talks about his research, he laughs often and clearly feels at home in his office, even though it’s still almost empty. At the moment there’s just a desk with two screens, a meeting table and an empty shelf. The room will fill up a little more, says the biochemist, who is currently moving from the University of Basel to ETH Zurich. For example, the shelf will soon feature drawings by his two children as well as postcards and congratulatory cards from colleagues. On the bare walls, the first thing he wants to do is hang two pictures of the discovery to which he owes his success: coloured microscope images of clusters of tumour cells. Metastases often grow from such clusters in cancer patients. The ETH Professor of Molecular Oncology has received numerous awards for his discovery of these cell clusters and their significance, including the recent Swiss Science Prize Latsis, which will be officially presented to him on 4 November of this year.
Knowledge from over a century ago
Aceto’s success story began in 2014. Back then, as a young postdoctoral fellow at Harvard Medical School in Boston, he examined blood samples from cancer patients and observed clumps of four or five connected tumour cells in them for the first time. He decided to investigate them further. Doing so was not the obvious choice, as many cancer researchers believed that metastases arise from individual circulating tumour cells (CTC). Such cells detach from the original or primary tumour and travel through the bloodstream to other parts of the body, where they sometimes take hold, divide and grow into metastases. With this already known, the cell clusters Aceto found were not necessary to explain metastasis formation. Nevertheless, rather than putting his discovery aside, he looked into it more closely.
First, he made sure that what he had observed wasn’t an isolated incident. Initial confirmation came from scientific publications more than 100 years old describing clumps of cells found in blood vessel sections. The authors called these “micro-emboli” and they suspected even then that their finding was related to the formation of cancer metastases. But such results couldn’t be refined for a long time because of the extreme dilution of cancer cells in the blood, as Aceto illustrates: “In 10 millilitres of patient blood, there are about 50 billion red blood cells and 50 million white blood cells floating around – but only a handful of tumour cells.” That’s why it wasn’t until the advent of microfluidic technologies, which can handle very small volumes of fluid and capture rare tumour cells with high precision, that researchers were able to efficiently detect and study cancer cells in blood samples.
Against the establishment
Using these methods, Aceto analysed blood samples from hundreds of cancer patients. He found that in sufferers who had such tumour cell clusters in their blood, the cancer progressed more rapidly than in patients with individual CTCs. In addition, in experiments with mice he showed that metastases grow 50 times more frequently from such cell clusters than from individual tumour cells.
Aceto thus upended the prevailing dogma that had viewed individual cancer cells as the seeds for metastases. However, publishing the results, which were surprising to the community, was difficult, and the review process was long and involved, Aceto recalls. But it wasn’t stressful for him, he says with a smile; on the contrary, he enjoyed it. Moreover, it was very challenging for reviewers to find fault with his data. It was eventually recognised and the work published in the prestigious journal