Histotripsy, a technique developed at the University of Michigan, has been approved by the US Food and Drug Administration for the treatment of liver tumors. This novel approach represents a promising alternative to cancer treatments such as surgery, radiation, and chemotherapy, all of which have significant side effects. HistoSonics, a company co-founded in 2009 by U-M engineers and doctors, was granted clearance today by FDA officials to use histotripsy to eliminate targeted liver tissue.

Since 2021, a human trial has been in progress at the U-M Rogel Cancer Center and other locations. It has been treating patients with primary and metastatic liver tumors using histotripsy, and it has successfully demonstrated the technology's effectiveness and safety in meeting the trial's primary objectives.

“Histotripsy is an exciting new technology that, although 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 trial at U-M.

HistoSonics can now actively market and sell its histotripsy delivery platform, known as Edison, to hospitals and medical professionals for liver treatments. The company's headquarters are in Minneapolis, and its advanced research and development operations are based in Ann Arbor.

Histotripsy works by creating microbubbles within the tumor with targeted ultrasound waves. The forces created by these bubbles as they form and collapse cause the mass to fragment, effectively destroying tumor cells and allowing the immune system to clear away the debris.

For patients, this could translate into treatment that avoids the physical toll of radiation or chemotherapy, minimizes concerns about drug compatibility, offers significantly shorter recovery times compared to surgery, and reduces treatment discomfort.

Histotripsy treatments are advantageous due to their ability to precisely target tumors, unlike radiation or invasive procedures. The Edison machine uses high-energy ultrasound waves to create bubbles, ensuring energy remains confined to the tumor, unlike radiation which affects all body parts.

Furthermore, the histotripsy system incorporates onboard diagnostic ultrasound imaging, similar to the kind used for prenatal imaging. This imaging is employed to plan and monitor the treatment in real-time, providing physicians with a live view of the "bubble cloud" and the tissue's response to therapy.

Histotripsy offers benefits that extend beyond tumor destruction. In the past year, two preclinical rodent studies have suggested that during the cleanup process, the immune system learns to recognize cancer cells as threats, potentially enabling the body to sustain its fight against the initial tumor and trigger a natural immune response to cancer.

In the first study, even when histotripsy destroyed only 50% to 75% of the liver tumor volume, the rats' immune systems successfully eliminated the remaining tumor with no signs of recurrence or metastases in over 80% of the animals.

Earlier this year, a second study demonstrated that histotripsy disrupts the cancer cell wall's "cloak," revealing proteins known as antigens that the immune system can use to identify threats. These antigens are typically removed during surgery or destroyed through chemotherapy and radiation. However, by breaking down the outer wall of cancer cells, histotripsy exposes these tumor antigens, allowing the immune system to identify and employ them 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 inventor of the histotripsy approach and a co-founder of HistoSonics.

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

Mendiratta-Lala, Xu, and the University of Michigan have a financial stake in HistoSonics. The company originated with backing from U-M's Coulter Translational Research Program and Innovation Partnerships, which serves as U-M's center for research commercialization.