A silicon chip the size of a business card could soon speed cancer diagnoses, track treatment more closely, and discover earlier signs of recurrences.
Researchers from Massachusetts General Hospital have developed a better technique for collecting and measuring the cells that escape from tumors and travel through the bloodstream, spreading cancer from one part of the body to another.
These so-called circulating tumor cells have been difficult to study, and little is known about them - but tracking them down has been a major goal of scientific research for decades.
In their research, published in the Dec. 27 issue of Nature, the Mass. General doctors say they have developed a chip that can find these tumor cells in a routine blood sample and allow them to be collected and studied.
"It could have a tremendous clinical impact," said Dr. Daniel Haber, director of the Mass. General cancer center and one of the researchers on the project. "It's hard to overstate the number of important applications it could have. It opens up a whole field of early detection for people with risks for cancer."
Circulating tumor cells are rare, even in patients with advanced cancers; there might be one tumor cell for every 1 billion blood cells. That means that researchers needed a lot of blood to detect even a few tumor cells. And previous technologies involved procedures that destroyed many of the tumor cells present in a blood sample.
"We have known that cancer cells are in circulation for centuries," said Mehmet Toner, director of the BioMicroElectroMechanical Systems Resource Center at Mass. General and the paper's senior author. "But people haven't been able to find these cells in large enough numbers in a routine fashion to be clinically useful."
The new process involves collecting three to five milliliters of blood from a patient - the same amount that is typically collected for routine blood tests. The sample is then put into a processor, which gently pumps the blood across the chip, which contains nearly 80,000 microscopic posts coated with antibodies that bind to tumor cells but not blood cells. At the end of the process, the tumor cells stuck to the chip can be counted with a computer imaging system or put directly under the microscope to be analyzed. The cells can also be broken open to extract molecular and genomic information.
The researchers tested the chip with 116 patients with advanced lung, breast, prostate, colon, and pancreatic cancer; the chip correctly found and collected circulating tumor cells in 115 of the cases. It also successfully identified the cells in a small group of patients with early prostate cancer.
The chip's high sensitivity could make it useful for finding early signs of cancer in healthy patients or relapse in cancer survivors.
"This is a step closer to having an instrument which can be used as a routine diagnostic test to pick up cancer in patients who feel perfectly normal and are in just for their annual physical," said Dr. Jonathan Uhr, an oncologist at the University of Texas Southwestern Medical Center who was not involved in the research.
The researchers also showed that the chip can be used to monitor the effectiveness of various cancer treatments.
As the patients' tumors shrank, so did the number of circulating tumor cells picked up by the chip. That means doctors can track patients' responses to anticancer drugs and switch treatment plans if their circulating tumor cell counts aren't dropping fast enough. (Currently, doctors follow treatment progress by monitoring the size of the tumor, but changes in tumor size take longer to show up than changes in circulating tumor cell count.)
Other technologies can measure and collect circulating tumor cells, but they are not nearly as sensitive as the new microchip and only work in 20 percent to 60 percent of patients with advanced cancer, Uhr said.
"The increase in sensitivity is a very important contribution," he said. The chip also allows scientists to study the captured tumor cells, potentially revealing new insights into how cancer spreads throughout the body, and whether the circulating cells have particular vulnerabilities that could lead to new treatments to target them.
The chips currently cost between $100 and $200 to manufacture, but if they are produced on a larger scale, Toner said, the cost could drop to just $10 to $30 per chip.
"It's not an expensive, out-of-reach technology," Toner said.
The chip, which has been licensed to a biotechnology company, is not ready for FDA approval, but Uhrpredicted that devices that count circulating tumor cells will be available fairly soon.
"In the next decade," he said, "there will be instruments that will be very effective at detecting tumors at an early stage."
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