The interstitial pressure inside a tumour is often remarkably high compared to normal tissues and is thought to impede the delivery of chemotherapeutic agents as well as decrease the effectiveness of radiation therapy.
While medications exist that temporarily decrease tumour pressure, identifying the optimal window to initiate treatment — when tumour pressure is lowest — remains a challenge. With support from NIBIB, researchers at Purdue University have developed a novel sensor that can wirelessly relay pressure readings from inside a tumour.
Tumours, like healthy tissues, need oxygen and nutrients to survive. In order to accommodate the demands of a growing tumour, blood vessels from surrounding tissue begin to grow into the tumour. Yet, unlike normal tissue, these newly formed blood vessels are disorganized, twisty, and leaky. It’s thought that the high pressure observed in tumours is a result of these abnormal blood vessels, which leak fluid and proteins into the area between tumour cells, known as the interstitial space.
In normal tissues, tightly regulated differences in pressure pull nutrients out of a tissue’s blood vessels and into the interstitial space, where they can be taken up by cells. Medications travelling through the blood also rely on these pressure differences in order to reach cells. When pressure in the interstitial space increases — as is the case in many tumours — medications are less apt to leave blood vessels. As a result, patients who have tumours with high interstitial pressure often receive a less than adequate dose of chemotherapy or other types of anti-cancer drugs. In addition, high interstitial pressure can also contribute to low oxygen levels in tumours. Because radiation therapy requires the presence of oxygen to be effective, tumours with high interstitial pressure are often less receptive to radiation therapy.
Window of Opportunity
Results from recent clinical trials and studies in animals suggest that a class of anti-cancer drugs called angiogenesis inhibitors may be able to temporarily reduce interstitial pressure and improve the efficacy of chemotherapy and radiation treatments. Angiogenesis inhibitors prevent the growth of new blood vessels and have long been investigated as a way to stop tumour growth. Recently, it has been hypothesized that there is a brief window after these drugs are given in which blood flow to tumours is actually normalised. This window provides an opportunity to more efficiently deliver chemotherapeutic drugs and radiation therapy.
However, because efficient methods for measuring interstitial tumour pressure are lacking, determining the optimal time to begin chemotherapy or radiation treatment within this normalization window remains a challenge.
“Right now, the only option for measuring pressure is to stick a needle inside the tumour. That’s not practical for clinical applications,” says Babak Ziaie, Director of the Biomedical Microdevices Laboratory at Purdue University.
A Wireless Pressure Sensor
After conversations with radiation oncologists with whom he collaborates, Ziaie decided to take on the challenge of creating a tumour pressure sensor. He was enticed by the novelty of the project. “No one had done this before,” said Ziaie. “No one was working on it or even attempting it.”
With support from NIBIB, Ziaie and his research team created a novel sensor that can be implanted into a tumour to wirelessly transmit interstitial fluid pressure readings. The sensor is an adaptation of a technology developed in the 1950s called the Guyton capsule, which is a perforated capsule that, once implanted, allows interstitial fluid to flow through it. Subsequent insertion of a needle into the capsule provides direct access to the interstitial fluid for pressure measurements.
Using special microfabrication techniques, Ziaie created a miniaturized wireless pressure sensor and combined it with a Guyton-like capsule so that it could generate interstitial pressure readings without the use of a needle and that could be read remotely.
Recently, Ziaie and his team tested the device by implanting it into pancreatic tumours in mice and were able to show a decrease in interstitial tumor pressure following administration of an angiogenic inhibitor.
“This is a great example of the power of convergence science,” said Tiffani Lash, Program Director for sensor technologies at NIBIB. “Integrating knowledge from the life and physical sciences with engineering concepts can help solve important clinical problems. It’s about thinking creatively to generate novel ways to treat disease.”