WeeklySA_AdminResilience: Scientists have used an automated laboratory system to test thousands of miniature tumours, identifying nine experimental drugs that weakened the rare “persister” cells believed to help cancers survive treatment and return…
By Own Correspondent
Cancer treatment can shrink or even appear to eliminate a tumour, only for the disease to return months or years later. Scientists have long suspected that a small group of unusually resilient cancer cells may be partly responsible.
Known as “persister” cells, these cells survive therapies that kill most of a tumour. They can later help to form new tumours, sending patients through further rounds of tests and treatment.
Researchers at the University of California, San Francisco (UCSF), have now developed a robotic laboratory system capable of studying thousands of miniature tumours at the same time. The system has revealed similarities among persister cells that could eventually help scientists develop treatments to eliminate them before cancer returns.
The findings were published in the scientific journal Science Advances.
Persister cells are extremely difficult to study because they may account for as few as one in every 1,000 tumour cells. They are also genetically identical to the other cells in the tumour, making them hard to identify through routine genetic testing.
Their ability to withstand treatment may also be temporary. By the time researchers remove the cells and grow them in a laboratory dish, the characteristics that enabled them to survive may already have disappeared.
“A few years ago, people were still asking whether persister cells were real,” said Dr Xiaoxiao “Vany” Sun, the study’s first author and an assistant researcher in UCSF’s Department of Pharmaceutical Chemistry.
“Now we can find them and test ideas for how to eliminate them.”
To speed up this work, the researchers built a robotic system that could perform about 10,000 experiments over the course of a week. Conducting the experiments manually would have been extremely time-consuming and could have produced inconsistent results.
The team collected 94 drug candidates that had previously been identified by other laboratories as possible treatments for persister cells.
Each drug was tested at different doses on miniature tumours representing two forms of lung cancer.
The tiny tumours were grown in laboratory plates containing hundreds of small wells and kept inside controlled incubators. A robotic arm moved the plates between different testing stations.
At one station, sound waves were used to place precise amounts of medicine onto each mini-tumour.
Researchers first applied a standard lung cancer treatment to kill most of the cancer cells. They then added an experimental drug to test whether it could destroy or weaken those that remained.
Other parts of the system stained the surviving cells with antibodies and took microscopic images, allowing researchers to identify, follow and measure persister cells throughout the process.
Of the 94 drugs tested, nine consistently weakened the surviving cells.
The researchers say this was an important finding because the persister cells had emerged under different treatment conditions. The results suggest that these rare survivors may share common weaknesses that could potentially be targeted with future medicines.
The findings do not yet represent a new treatment for patients. Further laboratory research and clinical trials will be required to establish whether any of the drug candidates are safe and effective in people.
However, the study provides scientists with a faster and more reliable way to investigate one of cancer treatment’s most persistent challenges: why some cells survive while others die.
Researchers now plan to expand the platform to study additional cancer types and a wider range of treatment conditions. They hope to build a large data resource that could help scientists predict which therapies are most likely to eliminate persister cells before they become permanently resistant to treatment.
“We expected each tumour to behave as its own special case,” said Professor Steve Altschuler, a UCSF professor of pharmaceutical chemistry and co-senior author of the study.
“Instead, we found patterns that held up across many different samples, suggesting there may be underlying rules that can help predict which therapies are most likely to work.”
If those patterns are confirmed through further research, doctors may one day be able to combine standard cancer therapies with treatments designed specifically to target persister cells.
Such an approach could potentially prevent the small number of surviving cells from rebuilding a tumour, reducing the risk of cancer returning and becoming harder to treat. – Science X
