Testing drugs on mini-cancers in the lab may reveal best treatment

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Written By Margonoe Tumindax

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Micrograph of human colon cancer cells in a three-dimensional extracellular matrix

TORSTEN WITTMANN/SCIENCE PHOTO LIBRARY

The next innovation in cancer treatment could be to test all possible drugs on thousands of miniature versions of a person’s tumour, grown in the lab, to see which works the best. The technique, sometimes called drug sensitivity testing, may have already helped a few children with advanced cancer live for longer than the standard approach.

It could eventually become routinely used for everyone with cancer, says Diana Azzam at Florida International University in Miami. “I would say it will help guide treatments in any [cancer], whether it’s aggressive or not.”

The cells used for growing the mini-cancers are obtained when someone has biopsies taken from their tumour or when they have surgery to remove the whole thing.

The approach means more than 100 different cancer drugs or combinations of drugs can be tested on thousands of clumps of cells grown in small dishes, using robotic equipment to apply them to each dish and nurture the cells for about 10 days. The treatment that proves most effective at stopping the cells from multiplying can then be used as a therapy.

Currently, doctors select whichever drug is usually employed against that cancer type or use their judgement to choose between a few options. If the first treatment fails to make the tumour shrink, a different drug would then be tried, but this trial-and-error process can take months and may have harsh side effects.

“Detrimental side effects occur that lower a patient’s overall health and make it much harder to continue treatment,” says Azzam. “The only way we can provide the right drug for the patient at the right time is to actually test drugs on tumour cells and find out which ones work and which don’t.”

The drug sensitivity testing approach has been in development for several years, but so far there has been only one previous trial, in adults with late-stage blood cell cancers, such as leukaemia. This work suggested that the technique lets people live for longer.

The new trial has found signs that the approach also helps children with solid tumours. Azzam’s team carried out this testing for 21 people with either tumours or blood cancers that had returned after multiple previous treatments, so had a poor prognosis.

The drug sensitivity testing led to a recommended treatment for 19 of the participants. Only six ultimately had the advised treatment because some doctors overrode the recommendation, while other children deteriorated too quickly and had to withdraw from the study.

Of the six who had the advised treatment, five had a remission of their cancer that lasted 8.5 times longer, on average, than after their previous cancer treatment.

It is reasonable to think this suggests drug sensitivity testing leads to a more potent treatment, because usually a cancer remission period lasts for a shorter time after each new cancer treatment is tried, says Maddy Parsons at King’s College London. “[Considering] it’s a relatively unsophisticated cell culture driven by the need for speed, it’s incredible how well it works.”

The next step is to see if the approach leads to better outcomes in a randomised trial, including in people who are diagnosed with cancer at a relatively early stage, who may get more benefit, says Azzam.

“There are always patients who will not respond to the first line of therapy,” says Parsons. “While they’re not responding, their cancer is getting worse. The goal is to predict right from the start who will respond to standard chemotherapy and who won’t, and what we should use instead.”

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