A novel cancer therapy that uses focused ultrasound to mechanically destroy tumors is offering new hope for patients, particularly those with inoperable liver cancer. The technique, known as histotripsy, operates without incisions, heat, or ionizing radiation, representing a significant advance in non-invasive treatment. By precisely targeting and pulverizing cancerous tissue, the procedure spares surrounding healthy organs and has been shown in some cases to trigger the body’s own immune system to fight the disease.
This emerging technology marks a fundamental shift from traditional ablation methods that rely on heating or freezing tissue. Instead, histotripsy harnesses the power of sound waves to create a highly controlled cloud of microbubbles that physically dismantles tumor cells into an acellular debris, which the body then absorbs over several months. The U.S. Food and Drug Administration approved the technology in 2023 for treating liver tumors, and clinical trials are underway to explore its efficacy in other organs and in combination with other cancer treatments like immunotherapy.
A New Approach to Tumor Ablation
For decades, physicians have used high-intensity focused ultrasound (HIFU) to destroy unwanted tissue with thermal energy, essentially cooking it from the inside. While effective, this method can sometimes damage healthy cells near the target area. Histotripsy, a term derived from the Greek words for “tissue” and “crushing,” is fundamentally different because it is a non-thermal and non-ionizing process. It uses pulsed sound waves to achieve a purely mechanical effect, physically breaking down the cellular structure of a tumor while leaving adjacent healthy tissue unharmed.
The procedure is guided by real-time imaging, such as ultrasound or MRI, allowing clinicians to monitor the treatment with great precision. Patients are placed under general anesthesia to control breathing and minimize movement, ensuring the ultrasound energy remains locked on the target. A robotic system then delivers the planned treatment, which can take anywhere from 10 to 50 minutes per tumor. The focused energy travels harmlessly through the overlying skin and organs until it reaches the tumor, where it initiates the destructive process. The resulting liquefied tissue is gradually cleared away by the body’s natural processes over one to two months, leaving behind minimal scarring.
The Mechanics of Microbubbles
The core of histotripsy’s effectiveness lies in a process called acoustic cavitation. The ultrasound device focuses sound waves with immense precision, causing a rapid series of negative and positive pressure changes within the targeted tissue. This acoustic energy agitates pre-existing nanometer-sized gas pockets naturally present in the tissue, causing them to expand and merge into a “bubble cloud” of microbubbles. These microbubbles oscillate, rapidly growing and collapsing with each ultrasound pulse.
The intense but highly localized mechanical strain produced by the oscillating microbubbles is powerful enough to rupture the membranes of nearby cells, effectively tearing them apart. This process reduces the complex structure of a solid tumor into acellular fragments. Researchers found that a key to controlling this process was using microsecond-length ultrasound pulses, which reliably generate the cavitation cloud only within the focal zone. This ensures the destructive forces are contained entirely within the tumor’s boundaries, providing a sharp and precise treatment margin.
Targeting Based on Physical Properties
Early research into similar technologies, sometimes called oncotripsy, revealed that cancer cells are physically different from healthy cells and may be more vulnerable to specific ultrasound frequencies. By carefully tuning the frequency and pulse duration, scientists could exploit the unique mechanical properties of tumor cells to cause their cellular skeletons to break down while leaving healthy cells intact. This principle underpins the safety profile of histotripsy, as it does not rely on molecular markers or require the tumor to be located separately from healthy tissues to be targeted effectively. The procedure has been successfully used on primary liver cancers, such as hepatocellular carcinoma, as well as on cancers that have metastasized to the liver from other parts of the body.
Stimulating a Systemic Immune Response
One of the most promising discoveries related to histotripsy is its ability to provoke an anti-tumor immune response. Many other cancer treatments, particularly those using heat or freezing, destroy tumor cells in a way that prevents the immune system from recognizing them. In contrast, the mechanical destruction caused by histotripsy appears to unmask tumor antigens, proteins that the immune system can identify as foreign. This process effectively turns the remnants of the destroyed tumor into an in-situ vaccine.
After treatment, immune cells flood the area to clean up the cellular debris, where they are exposed to these previously hidden antigens. This can lead to the activation of T-cells, a type of white blood cell that can then hunt down and destroy cancer cells throughout the body. This phenomenon, known as the abscopal effect, has been observed in preclinical studies where treating one tumor with histotripsy led to the shrinkage of other, untreated tumors. The levels of immune cell increase induced by histotripsy were significantly higher than those seen with radiation therapy or radiofrequency ablation.
The Path to Widespread Clinical Use
While histotripsy is currently FDA-approved only for liver cancer, its potential applications are vast. Preclinical studies have investigated its use in a wide range of organs, including the brain, kidney, pancreas, and prostate, as well as for cardiovascular diseases. Its non-invasive nature makes it an attractive option for patients who are not candidates for surgery or whose tumors are in difficult-to-reach locations.
Researchers are now focused on expanding its use through further clinical trials. One area of intense interest is combining histotripsy with immunotherapy drugs known as checkpoint inhibitors. The theory is that histotripsy can prime the immune system, making these drugs more effective at overcoming the defenses cancer cells use to hide from T-cells. Early data from a clinical trial in Spain showed that untreated tumors shrank at the same time as treated tumors, providing human evidence for the abscopal effect. As research continues, histotripsy may become a key tool in the fight against cancer, offering a way to not only destroy targeted tumors but also to unleash the body’s own power to heal itself.