November 9, 2022

Engineering better tumor models

Dr. Joshua Lang speaking to a congressman.

Dr. Joshua Lang, an oncologist specializing in genitourinary cancers, says bone metastases are a painful and common condition for men with metastatic prostate cancer.

The condition, caused by cancer spreading into a person’s bones, leads to serious complications like increased risk of broken bones, weakness and high levels of calcium in the blood. In addition to prostate cancer, it’s also a complication for patients with lung, breast, kidney, ovarian and thyroid cancers.

But even for as common as bone metastases are, researchers have a hard time studying it in a lab setting.

“Bone metastases are incredibly complex, with many different cell types involved,” said Lang, who also is an active researcher for UW Carbone Cancer Center. “It’s not just the cancer cells and the bone cells, there’s also immune cells and endothelial cells (found within blood vessels). And most of the animal models don’t spontaneously develop bone metastases either, so it’s really hard to study them.”

Lang has been working with Dr. David Beebe, a professor of biomedical engineering, and Dr. George Zhao, assistant professor in the department of human oncology, on using microscale and microfluidic devices to develop “tumor-on-a-chip” models of bone metastases.

The work traces back to a joint endeavor by the National Cancer Institute and the National Institute of Health to create a tissue chip consortium. These efforts focused on engineering small-scale models of living organ tissue on microchips. These are created with human tissue samples and structured to mimic the actual conditions and function within a person’s body.

“The idea is that we can recreate different humanized organs on a chip that would allow us to better understand the interactions between different cells, and then use those chips to test different drugs and treatments to better understand how a therapy might work for patients,” Lang said.

These chips are meant to create a more authentic human study environment for bench-top researchers and improve the odds those early results will perform as expected in advanced clinical testing. Lang also envisions real-time use of chips with patient treatment.

“That’s one of the things I’m most excited about,” Lang said. “While this is translational research, we’re also pushing the clinical research where we’re doing clinical trials and trying to create patient-specific environments on a chip that we can treat with the same drugs that we’re using with our patients in these trials, and we can see how well does it match the response in our patients.”

These chips would also allow researchers to study the unique aspects of tumor environment between different patients to tailor and target treatments.

“For one patient, their bone metastases might have a lot of immune cells in them, and maybe another patient has more bone cells. And we can really model all of those different types of environments we see in our patients,” he said.

This technology has broad tissue study applications and is also being explored at UW Carbone in kidney, lung and head and neck cancers. 

Lang said he and colleagues will continue to recruit patients for clinical trials to compare patient-specific chip function with the actual interactions in a patient’s body. Patient tissue donations, such as through WiscShare and the Precision Medicine Molecular Tumor Board, are a vital part of these efforts. 

“If it wasn’t for the donations of patients, we couldn’t learn about the new ways that cancer develops and becomes resistant to treatments,” he said. “That’s information that is going to help patients for years to come.”