Cancer News Information

Method developed at the University of Michigan offers a noninvasive substitute for surgery, chemotherapy, and radiation treatments for cancer

The U.S. Food and Drug Administration has sanctioned the utilization of sound waves to disintegrate tumors—a method termed histotripsy—in humans for liver treatment.

Pioneered at the University of Michigan, histotripsy presents a promising substitute for cancer treatments like surgery, radiation, and chemotherapy, which frequently entail notable side effects. Presently, FDA officials have granted approval to HistoSonics, a company co-established in 2009 by U-M engineers and doctors, for the application of histotripsy to eliminate targeted liver tissue.

A human trial in progress since 2021 at the U-M Rogel Cancer Center and other sites has managed patients with primary and metastatic liver tumors through histotripsy, illustrating the technology's ability to fulfill the trial's primary effectiveness and safety goals.

"Histotripsy is an exciting new technology that, even though it is in early stages of clinical use, may provide a noninvasive treatment option for patients with liver cancer. Hopefully, it can be combined with systemic therapies for a synergistic therapeutic effect," said Mishal Mendiratta-Lala, professor of radiology with Michigan Medicine and principal investigator on the U-M trial.

HistoSonics can now promote and sell its histotripsy delivery platform, named Edison, to hospitals and healthcare professionals for utilization in liver treatments. The company is headquartered in Minneapolis, with advanced research and development situated in Ann Arbor.

Histotripsy functions by employing targeted ultrasound waves to generate microbubbles within the tumor. The forces produced as these bubbles form and collapse result in the fragmentation of the mass, annihilating tumor cells and allowing the immune system to clear away the debris.

What this might signify for patients is treatment without the physical toll of radiation or chemotherapy, fewer concerns about drug compatibility, considerably briefer recovery periods than with surgery, and decreased treatment discomfort.

This is feasible because ensuring that histotripsy treatments accurately target the tumor, not healthy tissue, is much simpler compared to radiation or invasive procedures. Histotripsy relies on concentrating acoustic waves of high-energy ultrasound to form bubbles, and the Edison machine ensures that the energy is confined to the tumor region. Conversely, radiation impacts everything in its path through the body.

Furthermore, the histotripsy system integrates diagnostic ultrasound imaging, akin to that employed for visualizing babies in the womb. It is used for planning and monitoring the treatment in real time. Physicians have a live view of the "bubble cloud" and how tissue is responding to the therapy.

Histotripsy's potential benefits extend beyond tumor destruction. Over the past year, two preclinical studies in rodents suggest that during the cleanup process, the immune system learns to recognize cancer cells as threats. This can empower the body to persist in combating the initial tumor and activate a natural immune response to the cancer.

In the initial study, even after demolishing only 50% to 75% of the liver tumor volume through histotripsy, the rats' immune systems successfully eliminated the remainder, with no indications of recurrence or metastases in over 80% of the animals.

Earlier this year, a subsequent study demonstrated that histotripsy disintegrates the cancer cell wall's "cloak"—unveiling proteins that the immune system can deploy to recognize threats, referred to as antigens. These antigens are eliminated during surgery or eradicated during chemotherapy and radiation. By instead disassembling a cancer cell's outer wall, histotripsy exposes the tumor antigens for the immune system to identify and employ for targeted attacks on other cancer cells.

"We want to leverage histotripsy's immuno-stimulation effects and hopefully combine them with immunotherapy or drug delivery," said Zhen Xu, U-M professor of biomedical engineering, an originator of the histotripsy approach and a co-founder of HistoSonics.

"That will transition histotripsy from a local therapy into one that can treat tumors globally all over the body and eventually into a cure. In terms of cancer treatment, that will be the next step, and I feel very excited about the potential."

Xu and the University of Michigan have a financial stake in HistoSonics. The company was established with support from U-M's Coulter Translational Research Program and Innovation Partnerships, U-M's center for research commercialization.

The University of Michigan Histotripsy Group