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New Cancer Model Shows Promise in Predicting If Treatment Will Shrink Tumors

Posted by Paula Takacs Foundation
cells from cancer model shows promise

Will a specific cancer treatment actually work for a person diagnosed with cancer? Every person’s cancer is different, and even when a tumor has a genetic change for which there’s a matching targeted therapy, there’s no guarantee a given treatment is going to work.

But based on the results of a small study, funded in part by NCI, a team of researchers hopes to soon offer oncologists a new tool to guide treatment choices for their patients.

The tool is a new type of personalized tumor model, called micro-organospheres. And in a small study of eight people with advanced colorectal cancer, the researchers used the model to accurately predict whether the chemotherapy drug oxaliplatin would shrink their tumors.

Results from the study, led by Xiling Shen, Ph.D., the CEO of the biotechnology company Xilis, were reported June 2 in Cell Stem Cell.

To create the micro-organospheres, the research team takes tissue from a patient’s tumor biopsy and runs it through a desktop device, about the size of a standard printer. The end product: thousands of three-dimensional mini-replicas of the cancer suspended in tiny compartments on a lab dish.

Creating the models required much less tumor tissue than is usually required to grow other cancer models that use a patient’s own tumor tissue, Dr. Shen and his colleagues reported. And they were created quickly, in less than 2 weeks. That is much faster than similar models can be created, explained one of the study’s leaders, David Hsu, M.D., Ph.D., of the Duke Cancer Institute.

Their analyses also showed that the micro-organospheres largely retained the molecular features of the tumors from which they were created. And the models had many other components of the tumor’s surroundings, including immune cells and structural cells. The makeup of this tumor “microenvironment,” as it’s called, can influence how tumors respond to treatment.

The micro-organospheres “overcome a lot of the barriers” that have prevented similar tumor models from being used to help direct everyday patient care, Dr. Hsu said.

A larger study is being launched to determine whether these early findings hold up. Dr. Shen and Dr. Hsu, along with a third member of the team, Hans Clevers, M.D., Ph.D., of the pharmaceutical company Roche and a pioneer in organoid technology, jointly founded Xilis in 2019 to commercialize the technology.

The findings from this first study “are just a proof of concept,” Dr. Hsu acknowledged. “We need a larger study to … have the data needed to say if [these models] precisely capture patients’ response to treatment.”


From PDX and organoids to micro-organospheres

Cancer models, including tumor cell lines and animal models, are widely used research tools. They usually serve as generalized stand-ins for a specific type or form of cancer.

But over the past decade, researchers have taken these representations of cancer to the next level, developing personalized models created from individual patients’ tumor tissue. Efforts to create these patient-derived tumor models, as they’re called, are considered to be an important part of a concept known as precision oncology: treating a patient’s cancer based on its unique clinical and molecular features.

The two most common patient-derived models are mouse models called patient-derived xenografts (PDXs) and tumor-like cell clusters called organoids that are grown in lab dishes.

Because they grow as human tumors in living tissue, there was initially great hope that PDXs might be used to direct care for individual patients, explained Konstantin Salnikow, Ph.D., of NCI’s Division of Cancer Biology and who oversees NCI’s Patient-Derived Models of Cancer program.

But it soon became clear that because of certain limitations, in their current forms, PDX models may primarily be most useful as research tools and not to help direct the care of individual patients, Dr. Salnikow said.

Those limitations include the time it takes to establish them—a minimum of several months, and “sometimes up to a year,” Dr. Salnikow said. And because PDX mice lack functioning immune systems, he added, they can’t capture the important interactions between immune cells and tumors, which can influence how cancer treatments work.

Organoids, which are created using specific types of stem cells in tumor tissue, are grown in laboratory dishes. These models can be created somewhat more quickly and inexpensively than PDX models.

But when it comes to cancer, treatment typically needs to begin quickly after diagnosis, usually within a few weeks, said Dr. Hsu, who specializes in treating colorectal cancer.

Not only does creating organoids require a relatively large amount of tumor tissue—which isn’t always easy to come by—it also can take several months. In addition, the number of organoids produced is relatively small. For the time being, these factors may limit their potential for use in everyday patient care, he explained.

Micro-organospheres are intended to address both models’ limitations.

An electrical engineer by training, Dr. Shen developed the system for creating micro-organospheres at Duke. He recently left the university to lead Xilis full time.

The system’s lynchpin is a technology called microfluidics, which allows for precise handling of very small amounts of material suspended in specialized liquids. Producing the micro-organospheres also involves growing the collected cells in oil-based droplets, which required the researchers to develop a way to then remove the oil without harming the cells.

The entire process is highly automated and takes place in a small, desktop device. By automating production, the system eliminates much of the variability involved in growing organoids, which requires multiple manual steps, and streamlines the entire process, Dr. Shen explained.

As a result, he continued, there won’t be “different results depending on who cultured [the] cells.”

And rather than a just few organoids or PDXs, the product that emerges from the system is “thousands of miniaturized tumors,” Dr. Shen said, “and those mini-tumors are ready for drug testing within days.”

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Source: National Cancer Institute

Photo Credit: Image used courtesy of Xiling Shen

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