Noninvasive sound technology developed at the University of Michigan breaks down liver tumors in rats, kills cancer cells, and boosts the immune system to prevent future spread, potentially improving human cancer outcomes.

Sound Technology | Immune Systems | Tumors Killed in 25% to 50% of Cases

After just killing 50 percent to 75 percent of the liver tumor volume, the rats' immune systems were able to clear out the rest, with no evidence of recurrence or metastasis in more than 80 percent of the animals.

"Even if we don't target the entire tumor, we can still cause it to retreat and reduce the risk of future metastasis," said Zhen Xu, the study's corresponding author and a professor of biomedical engineering at the University of Michigan.

The University of Michigan's noninvasive sound technology breaks down liver tumors in mice, kills cancer cells, and strengthens the immune system to prevent future spread, potentially improving human cancer outcomes.

Tumors Killed in 25% to 50% of Cases | Sound Technology | Immune Systems | Tumors Killed in 25% to 50% of Cases

The immune systems of the rats were able to clear out the rest of the liver tumor volume after only killing 50 percent to 75 percent of it, with no evidence of recurrence or metastasis in more than 80 percent of the animals.

"We can still cause the tumor to retreat and lower the chance of future metastasis even if we don't target the entire tumor," said Zhen Xu, a biomedical engineering professor at the University of California, Berkeley.

The medicine also triggered the rats' immune responses, which may have helped to the tumor's eventual shrinkage and prevention of cancer from spread in the untargeted area.

Histotripsy is a non-invasive procedure that uses ultrasonic pulses to cause millimeter-level mechanical damage to target tissue. A relatively novel approach is now being used in a human liver cancer trial in the United States and Europe.

In many clinical circumstances, it is not possible to treat the entire tumor directly due to a variety of factors, including the size, location, and stage of a malignant tumor. To assess the repercussions of partially eradicating malignancies with sound, the current study targeted only a piece of each mass, leaving a viable full tumor. It also allowed the researchers from Michigan Medicine and the Ann Arbor VA Hospital to demonstrate the approach's success in less-than-ideal conditions.

"Histotripsy is a possible method that can overcome the constraints of currently recognized ablation modalities and produce safe and effective noninvasive liver tumor ablation," Tejaswi Worlikar, a doctoral student in biomedical engineering, stated. "We expect the results of this trial to drive more preclinical and clinical histotripsy research, with the ultimate goal of clinical acceptability of histotripsy treatment for patients with liver cancer."

Liver cancer is one of the top 10 cancer-related causes of death in both the United States and the rest of the world. Even with a wide range of therapeutic options, the prognosis is poor, with 5-year survival rates in the United States of fewer than 18%. The high likelihood of tumor recurrence and metastasis after the first treatment stresses the importance of improving liver cancer outcomes by therapeutic intervention.

Rather than using sound waves to create images of the interior of the body, U-M engineers have pioneered the use of those waves for treatment. And unlike existing procedures like radiation and chemotherapy, their technology has no detrimental side effects.

"Our transducer," Xu said, "delivers high amplitude microsecond-length ultrasound pulses — acoustic cavitation — to target the tumor selectively and break it up." "Traditional ultrasound equipment uses lower amplitude pulses for imaging."

The microsecond-long pulses from UM's transducer create microbubbles within the targeted tissues, which quickly inflate and collapse. These intense but tightly limited mechanical stresses break up the tumor's structure and kill cancer cells.

Xu's team at U-M has been pioneering the use of histotripsy in cancer research since 2001, culminating in the #HOPE4LIVER clinical trial sponsored by HistoSonics, a U-M spinoff company. Recent research by researchers on histotripsy treatment for brain therapy and immunotherapy has generated promising results.

The research was funded by the National Institutes of Health, the Focused Ultrasound Foundation, the Veterans Affairs Merit Review, the Forbes Institute for Discovery at U-M, and the Michigan Medicine-Peking University Health Sciences Center Joint Institute for Translational and Clinical Research.

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