It looks like a new ultrasound technique could selectively kill cancer cells according to research recently published in Applied Physics
Five years ago, Caltech’s Frank and Ora Lee Marble Professor of Aeronautics and Mechanical Engineering Michael Ortiz wondered if the physical differences between cancer cells and healthy cells might affect how they vibrate when bombarded with sound waves and how the vibrations might trigger cancer cell death. The physical differences included size, cell-wall thickness and the size of the organelles within them. Ortiz built a mathematical model to see how cells would react to different pulses and frequencies of sound waves. Working with then-graduate student Stephanie Heyden (Ph. D. ’14), he published a paper in 2016 in the Journal of the Mechanics and Physics of Solids showing that there was a gap in the resonant growth rates of healthy and cancerous cells. In theory, that meant a carefully tuned sound wave should cause the membranes of cancerous cells to vibrate to the point that they ruptured; leaving healthy cells unharmed. Ortiz calls the process “oncotripsy” from the Greek “oncos” for tumor and “tripsy” for breaking.
He subsequently applied for funding to continue the research through Caltech’s Rothenberg innovation initiative which supports research projects with high commercial potential. Ortiz also recruited doctoral student Erika F. Schibber (MS ’16, Ph.D. ’19) to work on the project. Her research involved the study of vibrations on satellites.
Ortiz then invited Professor of Aeronautics and Bioinspired Engineering Hans. W. Lipmann to attend a meeting of his research group. Gharib is a prolific inventor and has brought numerous research development from the lab to the market, including a prosthetic polymer heart valve and a smartphone app for monitoring heart health. Gharib was intrigued by the idea and pitched the project to advisee David Mittelstein, a graduate student in the MD-Ph.D. Program run by Caltech and the Keck School of Medicine at USC.
Mittelstein saw the opportunity to participate in the oncotripsy project from its conception to its proof of concept and got onboard. He put together a team to work on the project, including Caltech Professor of Chemical Engineering Mikhail Shapiro. Shapiro created a system to allow ultrasound to reveal gene expression in the body. He also designed bacteria that reflect soundwaves so they can be tracked through the body with ultrasound.
Ortiz was also connected to City of Hope Department of Immuno-Oncology Chair Eduardo A. Repetto, a physician-scientist who’s passionate about getting new treatments to patients. City of Hope researchers Jian Ye and oncologist M. Hourman Fekrazad also joined the team.
The research team hopes to show that ultrasound will kill cancer cells in a specific way that will also engage the body’s immune systems and arouse it to attack any cancer cells remaining following treatment.
With 50 million cells dying in the human body every day, most die naturally when cells grow old. This process is known as apoptosis. Other cells die as a result of injury or infection. A healthy immune system is able to tell the difference between apoptosis and injury and will rush to the site of injury to attack any invading pathogens.
If ultrasound can be used to cause cell death that looks like injury instead of apoptosis, white blood cells could flood the site of the tumor and attack remaining cancer cells.
While the testing has been done only in cell cultures in petri dishes, the study will expand to testing solid tumors and ultimately in living animals.
“This is an exciting proof-of-concept for a new kind of cancer therapy that doesn’t require the cancer to have unique molecular markers or to be located separately from healthy cells to be targeted. Instead we may be able to target cancer cells based on their unique physical properties,” said Mittelstein.
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About the author: Vikki Harmonay