Nine out of ten cancer patients die from metastases – this is how researchers want to prevent this

Cancer shows its worst side when you think you have conquered the disease. Then, when the original tumor is gone, but some cancer cells, which could not be affected by the therapy, awaken from their resting state. The cancer has spread, as the saying goes, to the liver, lungs, bones or brain. In many cases, the disease can no longer be cured.

Nine out of 10 cancer deaths do not die from the primary tumor, but from secondary tumors. If metastases could be suppressed, cancer would lose much of its horror.

Precisely for this reason, researchers are increasingly turning their attention to detecting cancer cells circulating in the bloodstream and on their way to metastasis.

Nicola Aceto is a biochemist and professor of molecular oncology at ETH Zurich, working on circulating tumor cells and their role in metastasis, especially in breast cancer. A few years ago, in a widely acclaimed study, he overturned the prevailing doctrine that a single circulating tumor cell could sow the seed for metastasis. According to Aceto, it is not the individual cells, but groups of up to fifty such cells that can develop into a metastasis.

This finding reveals a point of attack against metastasis: drugs that disrupt the clusters would slow metastasis. One of those drugs may be digoxin, as observed in animal studies by Aceto. Digoxin is one of the active ingredients in red foxglove, a poisonous plant traditionally used in Chinese medicine to treat cancer. In Western medicine, digoxin is used to treat cardiac arrhythmias.

The ETH is currently conducting a clinical trial with nine breast cancer patients in collaboration with the University Hospital Basel to investigate the drug’s mechanism of action. For this purpose, patients in whom clusters of circulating tumor cells could be detected receive a daily dose of digoxin that is adapted to their kidney function. The researchers expect to be able to present the results this year.

A study by French scientists has already pointed out that heart medication from the active substance group digitalis glycosides, which also includes digoxin, could improve the survival chances of cancer patients. They showed that cancer patients who received such heart drugs in addition to chemotherapy had an average 40 percent better life expectancy than those who received chemotherapy alone. “It is plausible,” says Aceto, “that the better survival rates were due to the destruction of the clusters of circulating tumor cells.”

A cancerous tumor can consist of billions of cells, very few of which leave the tumor and become circulating cancer cells. Ariel Ruiz i Altaba studies why some tumor cells do this and what mechanisms underlie this. He is a professor of medical genetics at the University of Geneva. He and his team recently discovered that cancer treatments of all things can promote the process of cell detachment. Strictly speaking, it is the therapies that aim to suffocate the tumor cells by depriving them of oxygen.

This coincides with a study by the research group led by ETH professor Aceto, which came to a similar conclusion: a lack of oxygen thus promotes the detachment of circulating cancer cells from the original tumour. That leads to a paradoxical situation, says Aceto: “If we supply the tumor with oxygen, there are fewer metastases, but the primary tumor grows faster.” This is a dilemma from which Ruiz i Altaba has discovered a possible way out.

The Geneva professor decoded the genetic signatures of pro-metastatic cells in tumors of deceased cancer patients. In the journal Cell Reports, he and his research group reported that those tumor cells that barely survive cancer treatment genetically reprogram themselves and set off a devastating cascade.

This starts with the reprogrammed cells causing a cytokine storm. As a result, neighboring tumor cells turn into migrating cells. And not only that: this fuels the cytokine storm even more and increases the migratory urge of the reprogrammed cells. “The cytokine storm is an important communication channel between cancer cells,” says the Geneva professor. If this signal transmission can be cut off, he suspects, the metastasis can be stopped. (aargauerzeitung.ch)