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

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

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

Thorston Wittman/Science Photo Library

The next innovation in cancer treatment may be to test all possible drugs on thousands of tiny human tumors grown in the laboratory to see which ones work best. This technique, sometimes called drug sensitivity testing, may have helped some children with advanced cancer live longer than standard methods.

Says it may eventually be used routinely for all cancer patients Diana Azam at Florida International University in Miami. “I would say it will help guide treatment for any (cancer), whether it’s aggressive or not.”

The cells used to grow microscopic cancers are obtained when someone takes a biopsy from a tumor or undergoes surgery to remove the entire tumor.

The method means more than 100 different cancer drugs or drug combinations can be tested on thousands of cell clumps grown in small petri dishes, using robotic equipment to apply them to each dish and culture the cells for about 10 days. The therapies proven most effective in stopping cell proliferation can be used as treatments.

Currently, doctors choose the drugs typically used to treat that type of cancer or use their own judgment to choose among several options. If the first treatment doesn’t shrink the tumor, different drugs are tried, but this trial-and-error process can take months and can have serious side effects.

“Harmful side effects can reduce a patient’s overall health and make it more difficult to continue treatment,” Azzam said. “The only way we can get the right drug to patients at the right time is to actually test the drugs on tumor cells and find out which ones work and which ones don’t.”

Drug susceptibility testing methods have been developed over several years; But so far, only one trial has been conducted before, adults with advanced blood cell cancers such as leukemia. The work suggests the technology could allow people to live longer.

New trials find signs that this approach could also help children with solid tumors. Azzam’s team tested this on 21 patients with tumors or blood cancers that had relapsed after multiple previous treatments and therefore had a poor prognosis.

Drug sensitivity testing provided treatment recommendations for 19 participants. Only six children ultimately received the recommended treatment, as some doctors overturned the recommendations and others worsened so quickly that they had to be withdrawn from the study.

Five of the six patients who received the recommended treatment experienced cancer remission that lasted 8.5 times longer than the average duration after previous cancer treatments.

It is reasonable to think that this shows that drug sensitivity testing can lead to more effective treatments, because cancer remissions typically last shorter after each new cancer treatment is tried. Maddie Parsons at King’s College London. “[Considering that]this is a relatively simple cell culture driven by the need for speed, it works incredibly well.”

Azzam said the next step is to see whether the approach leads to better outcomes in randomized trials, including in people who are diagnosed with cancer at a relatively early stage, where they may see more benefit.

“There are always some patients who don’t respond to first-line therapy,” Parsons said. “Although they are not responding, their cancer is progressing. Our goal is to predict from the outset who will respond to standard chemotherapy and who will not, and what we should use instead.”

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