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3D-printed tumor models could advance new cancer therapies

January 20, 2023 – Scientists have made great strides in the fight against cancer. The risk of dying from cancer in the United States has dropped by 27% over the past 2 decades, thanks in large part to researchers continuing to uncover the intricate details of how cancer works and making advances in treatment.

Now, the emerging technology of 3D bioprinting – like 3D printing for the human body, using real human cells – promises to accelerate this research, by allowing scientists to develop 3D tumor models that represent better patient samples.

The impact could be “enormous,” says Y. Shrike Zhang, PhD, assistant professor of medicine at Harvard Medical School and associate bioengineer at Brigham and Women’s Hospital, who studies 3D bioprinting. “It’s not the only technology that can enable in vitro tumor modeling, but it’s certainly one of the most capable.”

Why is this important? Because the 2D cell cultures that scientists often use today may not capture all the complexities of cancer growth, spread, and response to treatment. It’s one of the reasons why so few potential new cancer drugs — 3.4%, according to one estimate — can pass all clinical trials. Results may not be transmitted from the culture dish to the patient.

A 3D bioprinted model, on the other hand, can better copy the “microenvironment” of a tumor – all the parts (cells, molecules, blood vessels) that surround a tumor.

“The tumor microenvironment plays a critical role in defining cancer progression,” says Madhuri Dey, PhD student and researcher at Penn State University. “3D in vitro models are an attempt to reconstruct a [cancer] microenvironment, which sheds light on how tumors respond to chemotherapy or immunotherapeutic treatments when present in a native-like microenvironment.

Dey is the lead author of a study (funded by the National Science Foundation) in which breast cancer tumors were 3D bioprinted and successfully treated. Unlike some previous 3D models of cancer cells, this model did a better job of mimicking that microenvironment, Dey says.

So far, “3D bioprinting of cancer models has been limited to bioprinting individual cancer cells loaded with hydrogels,” she says. But she and her colleagues have developed a technique (called vacuum-assisted bioprinting) that allows them to control the location of blood vessels relative to the tumor. “This model lays the foundation for studying these shades of cancer,” says Dey.

“It’s pretty cool work,” Zhang says of the Penn State study (which he wasn’t involved in). “Vasculature is always a key element in [a] majority of tumor types. A model that incorporates blood vessels provides a “critical niche” to help tumor models reach their full potential in cancer research.

A 3D printer for your body

Chances are you’ve heard of 3D printing and own (or know someone who owns) a 3D printer. The concept is like ordinary printing, but instead of spitting ink onto paper, a 3D printer releases layers of plastic or other materials, hundreds or thousands of times, to build an object from from zero.

three-dimensional bio-printing works much the same way, except these layers are made up of living cells to create biological structures such as skin, vessels, organs, or bones.

Bio-printing has been around since 1988. Until now, it is mainly used in research settings, such as in the field of regenerative medicine. Research is ongoing for ear reconstruction, nerve regeneration and skin regeneration. The technology has also recently been used to create eye tissue to help researchers study eye disease.

The technology’s potential for use in cancer research has yet to be fully realized, Dey says. But it can to be changing.

“The use of 3D bioprinted tumor models is approaching translations in cancer research,” says Zhang. “They are increasingly being adopted by the research field, and [the technology] began to be explored by the pharmaceutical industry for use in cancer drug development.

Because bioprinting can be automated, it could allow researchers to create complex, high-quality tumor models on a large scale, Zhang says.

Such 3D models also have the potential to replace or reduce the use of animals in tumor drug testing, Dey notes. They “should provide a more accurate drug response compared to animal models because animal physiology does not match that of humans.”

The FDA Modernization Act 2.0a new US law eliminating the requirement that drugs must be tested on animals before humans has “paved the way for such technologies in the drug development pipeline,” Zhang said.

What if we could create a personalized tumor model for each patient?

The possible uses of bioprinting go beyond the lab, Dey says. Imagine if we could customize 3D tumor models based on individual patient biopsies. Doctors could test many treatments on these patient-specific models, allowing them to more accurately predict how each patient would respond to different therapies. This would help doctors decide which treatment is best.

In Dey’s study, the 3D model was treated with chemotherapy and immunotherapy, and it responded to both. This highlights the potential for these 3D models to reveal the body’s immune response and be used to screen for therapies, Dey says.

“We hope that in the future, this technique can be adapted to the hospital, which would speed up the course of cancer treatment,” says Dey.

To that end, she and her colleagues are now working with real breast cancer tumors taken from patients, recreating them in the lab in 3D for use in chemo and immunotherapy screening.

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