The patient went into complete remission for nearly five months. But about eight months after she started eribulin treatment, the cancer returned and she passed away.
This is often true for the extremely aggressive cancers Welm studies. But she is encouraged by two key oncological metrics from this patient’s treatment: “progression-free survival” (how long a drug keeps cancer from spreading) and “time to next systemic therapy” (how long until another drug is needed). Both numbers usually go down with each subsequent round of treatment. In this case, they went up. The patient’s previous chemotherapy had stopped the cancer from growing for 41 days. The eribulin gave the patient 138 days before the cancer returned, and 197 days before she needed a new kind of treatment.
It’s important to note that this is a proof-of-concept study, and it represents only one person. Still, says Lim, “it's certainly brought us one step closer to making these avatars more potentially useful to the clinical world.”
Specifically, it shows that organoids are a reliable alternative to testing on mouse xenografts, which can be slow and expensive. That process can take up to a year, and it doesn’t always work. “Patients who have late-stage disease don't have that time,” Lim says. Organoids are faster to scale up, since they don’t require animals. Welm is shooting to run these tests in about 12 weeks, start to finish. With organoids, says Lim, “the sky's your limit. You can test as many drugs as you want.”
Still, there are other caveats. Whenever scientists study cancer outside the human, an immune system is missing. Welm uses immune-compromised mice, and organoids grow without immune challenge. For the time being, that makes these models incompatible with testing immunotherapies, or drugs that rally the natural immune system to combat cancer, Lim and Welm agree.
But that limitation is fading too, says Tony Letai, a professor at Harvard Medical School and the Dana Farber Cancer Institute. Researchers are learning to culture organoids in blood, or in tandem with immune cells. “The writing's on the wall that it ultimately will be possible,” says Letai, who is also president of the Society for Functional Precision Medicine. Just 20 years ago, growing real tumors in the lab was a crapshoot—they didn’t reliably emulate the patient’s. Today, not only are they accurate matches, but scientists can keep cultures alive for months, they have dozens of more potent drugs to screen, and they can analyze the biology of individual cells with mind-boggling accuracy. “This type of approach is, I think, the future of finding cancer patients the right drugs,” Letai says.
The University of Utah team has begun enrolling patients in a related clinical trial, in which they will match people to drugs based on the organoid versions of their tumors. The trial includes a survey for physicians as well—Welm hopes to find out whether doctors would actually trust the tool. “It looks very promising, but we don't know till we know,” she says.
Welm remembers that even in 2019, when her team was awed by the medical scans showing the patient's improvement after receiving eribulin, they knew the likely outcome. “We have a guarded enthusiasm, just because we know that we need better therapies,” she says. “We have a lot of questions that we still need to answer.”
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