Rice-led research discovers focused ultrasound enhances cancer-killing effects of protein therapy

An innovative mechanotherapy approach combination of low intensity focused with trail protein shows a significant reduction in prostate cancer tumors through synergistic activation of cell death pathways.

A collaboration study led by researchers from the University of Rice and the University of Vanderbilt has shown that combining protein therapy called ligand (trail) Apoptosis inductor related to the tumor necrosis factor with focused ultrasound (FUS) can significantly reduce the size of the tumor in prostate cancer models. The research, published in the Advanced Science magazine on February 21, 2025, represents the first evidence that the low intensity mechanical force combined with trail can treat effective cancers.

“There is an urgent need to improve the way we treat advanced and recurring prostate cancer, which is the second cause of death leading death among men in the United States and is the most frequently Cancer cancer (, to the right of a specific form of cancer (, to the right of a form of cancer, “, to the right of a form of cancer. Find promising that we have hopes can be translated for clinical care.”

The challenge with current cancer treatments
Current standard treatments for prostate cancer often come with serious adverde effects. High intensity ultrasound (HIFU) therapies have drawn attention for their ability to specifically direct tumor tissue, but still cause unwanted side effects such as skin burns and urinary complications.

Trail protein specifically indicates death in cancer cells while avoiding healthy cells. However, despite the promising laboratory results, clinical trials with trail have limited success due to their very short half -life in circulation (approximately 30 minutes).

“Previously, we had found certain mechanical forces such as the cutting effort of fluid could amplify the anti -cancer effects of the path with an influx of calcium and the activation of a protein called Piezo1 that triggered cell death,” King explained. However, the sharp fluid effort is only present in circulatory and lymphatic systems, which makes it ineffective against solid tumors.

How ultrasound focused improves the effects of killing against trail cancer
The researchers discovered that intensity -centered ultrasound (LIFU) can activate mechanical pieces, a typing ionic channel that improves trail cancer killing skills. This activation allows calcium to enter cancer cells, triggering the intrinsic apoptosis pathway (cell death).

Using prostate cancer lines, graduated students Abigail Fabiano and Malachy Newman conducted experiments to optimize ultrasound parameters while ensuring that nearby healthy cells are not relaxed. The team discovered that combined Fus and Trail therapy was much more effective than any of the treatment alone.

“As the fus pressure increased, trail mediated apoptosis increased more particularly in PC3 cells compared to LCAPA cells,” says the authors in the document. This is significantly due to the fact that PC3 cells represent a more advanced metastatic state of prostate cancer than LN-CAP cells, a suggestion that therapy could be effective aggressive forms of the disease.

The researchers confirmed that the mechanism behind this improved effect implies the activation of Piezo1 by:
Demonstrating reduced effectiveness when they blocked calcium with chelating agents
Use of pharmacological inhibitors or typing ionic channels
Performing genes of genes elimination directed to Piezo1
“These results exemplify that the interruption of Piezo Mecanoactivation affects the effectiveness of this combined therapy to induce apoptosis,” the authors point out.

Impressive results in animal models
When tested in mice models, combined therapy significantly reduced tumor load compared to fus or trail alone. The researchers administered two treatments, six days apart and monitored tumor growth for 62 days.

On the 62th cell inoculation after the tumor, the average volume of tumors treated with combined therapy was 529 ± 170 mm³, significantly narrower than tumors treated with individual control or treatments. It is important to note that the researchers did not find evidence of harmful thermal effects or damage to surrounding tissues.

“In general, a greater expression of Piezo1 correlated with a lower tumor load in vivo, and decreased for the fus condition,” report the authors. “Taking into account that Piezo1 is elevated in PCA, this could indicate that the mechanical fus effects can only activate and regulate the potential expression of Piezo1 approximately time.”

The team also examined different time intervals between the injection of trails and exposure to the FUS, finding that the immediate application (0 hours) and the 4 -hour intervals produced the best results in the reduction of tumor growth.

Clinical Translation Potential
“This mechanotherapy sacrifices a clinical translator approach when using AVIA FUS technology, applicable to treat additional types of cancer,” conclude the authors. The approach has several advantages over existing therapies:

• Use low intensity fus, avoiding thermal ablation and damage associated with greater intensity treatments
• Therapy is not invasive and is precisely objective
• Activate the death paths of cancer cells while avoiding healthy cells
• The mechanical index used was well below the safety limits of the FDA

“The development of non -vasive, safe and effective treatment options for PCA is very necessary, considering the risk that other therapeutic options impose on the patient’s quality of life,” says the authors in their discussion. “Mecanotherapy presented here exemplifies how FUS can aim at tumors and improve the pro -elptototic effects of the Solble Path.”

Future instructions
Researchers suggest that this approach could be combined with other cancer therapies or modified to treat different types of cancer. Technology is particularly promising because the focused ultrasound equipment is already widely warned in clinical environments.

“This fundamental study provides crucial preclinical ideas that can be used to develop a new combination therapy for prostate cancer,” King said. “In addition, it opens the doors to many new roads to use mechanotherapy in medicine and has a large amount in how FUS and other mechanical therapies can be combined with small molecule protein therapy and advertising of medications in the future of ads.”

The research team believes that this mechanotherapy could easily translate to examine success in the treatment of other types of cancer, including those that are difficult to deal with conventional methods.

Reference:
Fabiano, Ar, Newman, MW, Dombroski, yes, et. Alabama. (2025). Applying ultrasound to sensitize mechanical prostate tumors and not invasively to apoptosis using the path. Advanced Science, 2412995. Https://doi.org/10.1002/advs.202412995