A promising approach to achieve safer, more effective, and more precise breast cancer treatment has earned a University of Virginia researcher a new $5.5 million grant.
Natasha Diba Sheybani, an assistant professor of biomedical engineering and research director of the Focused Ultrasound Cancer Immunotherapy Center at UVA, is pioneering an approach to metastatic breast cancer treatment that transforms sound waves into active medical instruments.
Her work with focused ultrasound earned her the U.S. Department of Defense Breast Cancer Research Program Era of Hope Scholar Award, designed to support innovative, early career researchers with potential to transform breast cancer treatment and be leaders in the field of breast cancer research and patient advocacy. Sheybani is the University's first-ever recipient of this coveted award - there was only one Era of Hope Scholar Award granted nationwide in fiscal year 2024.
With only about a third of patients living past five years from diagnosis, metastatic breast cancer remains incurable. Chemotherapy, radiation, surgery and newer therapies can slow its spread, but they also take a heavy toll on the body - often introducing safety risks and off-target toxicities to healthy tissues.
For many patients, these treatments buy time rather than remission. That's where Sheybani's work with a safe, emerging interventional tool comes in. Focused ultrasound, or FUS, is not only poised to advance cancer treatment research, but it's also set to enable an approach that puts long-term survivorship of the patient front and center - aiming to target cancer with greater precision and fewer side effects.
Using sound to speak the body's language
Sheybani's research has previously revealed how sound waves can become sophisticated communicators with the body's immune system. FUS technology, which uses ultrasonic waves for therapy, is a highly versatile tool that Sheybani's lab now explores to:
- 'Speak' directly to tumor barriers to create precise pathways for therapy: Many cancer treatments struggle to penetrate the fortress-like defenses of tumors, which often shield themselves from drugs and cytotoxic immune cells. FUS can be tuned to disrupt these barriers without surgery or radiation, allowing treatments to reach their targets more effectively.
- Guide therapeutic 'messages' straight to cancer cells: Instead of flooding the body with chemotherapy, which can harm healthy tissue, FUS directs treatment only where it's needed. By using sound waves as a precision delivery or tumor-specific destruction tool, Sheybani's method may help reduce side effects and improve efficacy in the long term.
- Signal the immune system to mount a targeted response: The immune system often struggles to recognize and attack cancer cells. FUS can act like a megaphone, alerting the body's natural defenses to the presence of cancer and enhancing the effectiveness of cancer immunotherapies.
We're essentially programming the physics of sound waves to communicate with complex biology inside the human body. Breast cancer incidence is on the rise, particularly among younger women, which means we need less toxic, less invasive treatment options now more than ever. We hope to re-imagine the paradigm for care and survivorship by engineering FUS to overcome key bottlenecks in breast cancer treatment."
Natasha Diba Sheybani, assistant professor of biomedical engineering and research director of the Focused Ultrasound Cancer Immunotherapy Center, UVA
4 ways sounds waves could transform cancer treatment
Sheybani's research explores multiple innovative ways to use FUS to outsmart cancer.
- Thermal Ablation: Turning Up Signal Strength
FUS can deliver a precise thermal signal to cancer cells, heating them up until they break down - without harming the surrounding healthy tissue. This method transmits a direct and destructive message to tumors, offering a non-invasive strategy for tumor "debulking." Notably, this approach is under investigation across multiple first-in-human clinical trials at UVA that Sheybani interacts with closely.
- Mechanical Ablation: Disrupting Tumors With Sonic Shocks
Some tumors won't listen to gentle persuasion, so ultrasound delivers a powerful disruptive signal, using pulses of sound waves to break apart stubborn cancerous structures. This approach is especially promising for deep-seated or dense tumors that resist other treatments.
- Sonodynamic Therapy: Activating Cancer Drugs With a Sonic Cue
Some drugs only work when given the right signal - and focused ultrasound can be that trigger. By activating specialized cancer drugs at exactly the right place and time, this method ensures medicine works only where it's needed, reducing toxicity and boosting effectiveness.
- Barrier Opening: Creating a Clear Line of Communication
The blood-brain barrier and other protective layers often block essential cancer treatments, like a locked door keeping medicine out. Focused ultrasound acts as a temporary passcode, briefly opening pathways so drugs can reach their targets - with barriers recovering once delivery is complete.
"This grant will deepen our efforts to tackle not only primary breast tumors, but also metastases. We are taking a close look at multiple FUS mechanisms of action that are clinically ripe and confronting tough questions like 'How do we know when we've treated enough?' or 'How do we decide if we need to shift the course of treatment?' To answer these questions, we will harmonize FUS with customized tools for monitoring biological responses in real-time," Sheybani said. "We hope that these novel strategies will allow us to truly deliver on the promise of precision intervention with this technology."
The Era of Hope Scholar Award will also support a new initiative in collaboration with the UVA Cancer Center that Sheybani will lead - bringing together cancer survivors, caregivers and patient advocates for critical conversations with clinicians, researchers and trainees committed to enabling meaningful translational strides in cancer research.
Amy Bouton, Harrison Distinguished Teaching Professor Emerita of Microbiology, Immunology, and Cancer at the School of Medicine and former inaugural associate director for education and training at the UVA Cancer Center (2014-2023), highlighted the significance of the award:
"As someone who has served on the Department of Defense Breast Cancer Research Program's parent committee, I know just how rare and exceptional it is for a researcher to receive this honor. The Era of Hope Scholar Award isn't just about recognizing talent - it's about supporting scientists who are pushing the boundaries of what's possible in cancer research. Dr. Sheybani's work is exactly the kind of innovative science this award was designed to elevate."
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