Metastatic disease is overwhelmingly responsible for cancer-related deaths, accounting for 90% of fatalities. Using existing drugs, researchers at the University of Basel may have found a strategy that stifles the spread of malignant circulating tumour cells (CTCs), the harbingers of the spread of cancer.
In the mid 19th century Australian pathologist Thomas Ashworth hypothesized that CTCs — cancerous cells that break away from a primary tumor and enter the bloodstream — were a fundamental prerequisite to metastasis. But isolating them was a big challenge, akin to the proverbial needle in a haystack as they are extremely rare, even in patients with advanced metastatic cancers (estimated at one CTC/billion normal blood cells), although recent technological advances have allowed for their detection, the Basel-based researchers noted in the journal Cell.
While Nicola Aceto worked as a postdoctoral fellow at Harvard Medical School, he found that circulating tumor cell clusters — not single cells — are typically the culprits with the firepower to trigger metastasis.
Aceto then spearheaded the formation of the Cancer Metastasis Lab at the University of Basel, leading a team of researchers who found that these clusters can mimic certain properties of embryonic stem cells, including the ability to proliferate and develop into tissue. However if these clusters are dissociated, these properties could be vanquished, they found, which prompted the search for substance that can quash such metastasis development by dissociating CTC clusters.
”We thought of acting differently from standard approaches, and sought to identify drugs that do not kill cancer cells, but simply dissociate them,” Aceto said in a statement.
The researchers used technology from UK-based ANGLE to identify clusters in patient blood, and consequently patients whose cancer would likely spread. In a study with mice, the team then tested 2486 FDA-approved drugs to ascertain their impact on breaking up these CTC cell clusters into individual cells. A small group of drugs were found capable: Treated mice experienced an 80% reduction in metastasis compared with untreated animals, with the metastatic spread of cancer virtually eliminated in treated animals.
The team is now expecting to test the chosen drugs in patients with breast cancer — a form of cancer that easily metastasizes — in a clinical trial this year. The approach of preventing metastasis instead of indiscriminately killing cancer cells, if successful, could potentially prove an improvement in terms of toxicity and side-effect profile versus conventional treatments such as chemotherapy and immunotherapy, the scientists say.
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