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A groundbreaking study published in Advanced Science reveals that combining an existing small-molecule protein therapy, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), with focused ultrasound (FUS) can significantly reduce tumor size and burden in prostate cancer models. The research, conducted by scientists at Rice University and Vanderbilt University, highlights a novel approach that could revolutionize prostate cancer treatment.
Addressing a Global Health Crisis
Cancer remains one of the leading causes of death worldwide, with approximately 10 million fatalities annually. This collaborative study was led by Michael King, the E.D. Butcher Professor of Bioengineering in the George R. Brown School of Engineering and Computing at Rice University, and Charles Caskey, associate professor in radiology and radiological sciences at Vanderbilt University. Their work marks the first instance where low-intensity mechanical force, in combination with TRAIL, has been demonstrated as a viable cancer treatment.
The research sheds new light on how low-intensity FUS and soluble TRAIL specifically target and destroy cancer cells within the compact environment of primary prostate cancer lesions, offering hope for improved therapies.
The Urgent Need for Better Prostate Cancer Treatments
“There is an urgent need to improve how we treat advanced and recurrent prostate cancer, which is the second-leading cause of death among men in the United States and the most frequently diagnosed cancer in more than 100 countries,” said King, a Cancer Prevention and Research Institute of Texas Scholar. “We have now found a safe, effective, and noninvasive way to enhance the antitumor effects of TRAIL, a promising finding that we are hopeful can soon be translated for clinical care.”
Conventional prostate cancer treatments are often associated with severe side effects. In recent years, FUS-based therapies have gained attention for their ability to target tumor tissue with minimal off-target effects. This study further supports FUS as a promising method to enhance the effectiveness of TRAIL in treating prostate cancer.
How the Combination Therapy Works
TRAIL is a protein that induces the death of cancer cells while sparing healthy cells. However, its effectiveness in clinical trials has been limited due to its short half-life of about 30 minutes, requiring frequent administration that increases the risk of side effects.
“Previously, we had found that mechanical forces like fluid shear stress (FSS) could amplify the anticancer effects of TRAIL by triggering an influx of calcium and activating a protein called Piezo1, which initiates cancer cell death,” King explained.
However, FSS is not applicable to solid tumors, as it only exists in the circulatory and lymphatic systems. This limitation prompted researchers to investigate whether FUS could be used as a localized mechanical force to enhance TRAIL’s cancer-killing effects in solid tumors.
Laboratory Success and Future Implications
Graduate students Abigail Fabiano and Malachy Newman, under the mentorship of King and Caskey, performed experiments using prostate cancer cell lines to refine and optimize FUS parameters. Their initial goal was to ensure that healthy cells remained unharmed while cancer cells were effectively targeted.
The results demonstrated that the combination therapy of FUS and TRAIL was significantly more effective in reducing cancer cell numbers and tumor size compared to using either treatment alone. This supports the hypothesis that TRAIL and FUS-mediated Piezo1 activation work synergistically to maximize tumor reduction.
“This foundational study provides crucial preclinical insights that could lead to a novel combination therapy for prostate cancer,” King stated. “Furthermore, it opens the doors to many new avenues in mechanotherapy and has far-reaching implications for combining FUS with other small-molecule protein therapies and drugs to treat various types of cancer with fewer adverse effects.”
Looking Ahead
As the scientific community continues to explore novel treatments for prostate cancer, this study underscores the potential of combining protein therapy with mechanical forces like FUS. While more research and clinical trials are needed before this therapy becomes widely available, these findings offer a promising step toward more effective and less invasive cancer treatments.
Disclaimer: This article is for informational purposes only and does not constitute medical advice. Patients should consult with their healthcare providers before considering any new treatments.
