Cancer becomes deadly mostly in its advanced stages, when it begins to spread throughout the body and form new tumors. “Nine out of ten cancer deaths are due to metastatic disease,” says Nicola Aceto, professor of molecular oncology at ETH Zurich. For this reason, the biologist, originally from northern Italy, focused on studying cancer cells after completing his doctorate at the Friedrich Miescher Institute for Biomedical Research in Basel. These cancer cells detach from tumors, enter blood vessels, and attempt to establish themselves in other parts of the body.
Dissolving cell clusters with a drug
Such circulating tumor cells are extraordinarily rare compared to normal blood cells. During a three-year research stint as a postdoctoral fellow at Harvard Medical School in the United States, Aceto first had to develop sophisticated methods to find the proverbial needle in the haystack in patient blood samples. Then, ten years ago, he made a groundbreaking discovery: not only do single cells detach from tumors in the breast, but sometimes entire clusters of dozens of cells break off. These clusters find it much easier than single tumor cells to form metastases in new locations in the body.
Aceto subsequently returned to Switzerland, where he established his own research group at the University of Basel in 2015. Through experiments on mice, he and his team found that these cell clusters could be dissolved using a drug called Digoxin. While entirely unknown in cancer treatment, Digoxin had been used for decades in cardiology to treat arrhythmias. Aceto and his team wanted to investigate whether the encouraging results from animal experiments could also apply to humans. To this end, the researchers collaborated with doctors at the university hospitals in Basel and Zurich, as well as the Cantonal Hospital in Liestal.
“The clinical study has now been completed. We’ve just submitted the results to a scientific journal,” says Aceto, who moved with his team to ETH Zurich in early 2021. Because the study’s results have yet to be published, he is reluctant to share too many details but reveals: “Patients with advanced breast cancer participated in the study. We demonstrated that Digoxin treatment can indeed partially dissolve circulating tumor cell clusters in the blood,” Aceto says. “The clusters became smaller, but they were not completely gone.” These promising results motivate him to continue on this path. Aceto recently founded a spin-off company aimed at developing substances that work even better than Digoxin. “That will, however, take a few more years,” he notes.
Decoding unknown signals
In the meantime, he and his team are addressing numerous other questions related to the spread of tumors. A significant portion of this research is funded by donations, for which Aceto is “truly very grateful.” This support enables them to delve into the mechanisms of metastasis and identify new treatment options that could halt or even prevent the deadly progression of cancer.
Recently, Aceto and his team published findings suggesting that the internal clock controls the detachment process from tumors: far fewer cancer cells travel during the day compared to the night, when the rest of the body is at rest. For Aceto, this doesn’t mean cancer patients should stop sleeping but rather that cancer cells seem to wait for signals before detaching. “We aim to decode these still-unknown signals,” says Aceto. With this knowledge, it may someday be possible to prevent cancer cells from traveling at night, thereby inhibiting the formation of metastases.
In a new project funded by the Swiss Cancer Research foundation, Aceto and his team are opening another research avenue. They aim to expand their findings on circulating cell clusters, which thus far have focused exclusively on breast cancer, to other types of cancer. In collaboration with specialists from Heidelberg University Hospital, they are now investigating cell clusters shed into the bloodstream by pancreatic tumors. “This is a very aggressive cancer type that often spreads metastases and, unfortunately, still usually proves fatal within a few years,” says Aceto. “For these patients in particular, it’s crucial to probe the weaknesses of circulating tumor cells and look for new therapeutic targets.”