Sorting Circulating Tumor Cells
About This Podcast
NIBIB grantee Mehmet Toner of the Massachusetts General Hospital Cancer Center describes his work to create a chip that can sort circulating tumor cells (CTS), which break off tumors into the bloodstream and are responsible for metastasis, from other types of cells found in the blood. Detection of CTS can play an important role in early diagnosis, characterization of cancer subtypes, and treatment monitoring.
This is a production of the National Institute of Biomedical Imaging and Bioengineering, part of the National Institutes of Health
Host: Margot Kern
Toner: The benefits of finding circulating tumor cells is multifold. It could really turn cancer into a manageable disease.
Kern: You’re listening to Mehmet Toner, a professor of biomedical engineering at Harvard University, who led the development of a microfluidic device that can isolate circulating tumor cells from whole blood samples.
Kern: Circulating tumor cells, also known as CTCs, are cells that have broken off a solid tumor and entered the blood stream. While most CTCs die in the blood, a small percentage can become embedded into tissues of distant organs where they can begin to form a new tumor. This is how cancer spreads or metastasizes.
Kern: But, despite their ill-effects, these cells have a silver lining. The presence of CTCs in the blood can actually help doctors monitor whether a particular treatment is working.
Toner: If the circulating tumor cell number goes up or down as the patients are on treatment, you would know very quickly from the blood test.
Kern: In addition to monitoring CTC number in the blood, the DNA of circulating tumor cells can be analyzed to look for cancer-causing mutations, information that can be used by doctors to determine what medications may be most effective.
Toner: Most drugs now, almost exclusively, all new drugs are based on targeted therapy where patients with specific mutations respond to specific treatments, targeted treatments, that are less toxic, much more effective.
Kern: The advantage of analyzing CTC DNA is that information about a specific tumor can be procured from the blood, thus, negating the need for a tissue biopsy, a procedure that can be extremely painful for some patients and difficult to carry out.
Toner: So you’re doing a liquid biopsy, in a sense. You find these cells in blood and then look at their genomic makeup and decide what drug they should be put on.
Kern: Sounds simple enough. Well, it would be if it weren’t for the fact that circulating tumor cells are nearly impossible to catch.
Toner: They are one in a billion, one in 10 billion, so it’s really looking for a needle in a haystack, if not worse.
Kern: To give you an idea of the size of this haystack, for every milliliter of blood, there are a few million white blood cells, around a billion red blood cells, and only between 1 and 10 circulating tumor cells. Those are pretty tough odds, but it turns out they’re not insurmountable.
Kern: Over the past several years, Toner has worked to develop a microfluidic chip that can separate the rare and valuable CTCs from the billions of other cells found in a patient’s blood.
Toner: The way we find these cells is when you go to a physician’s office, you give a tube of blood, that tube of blood goes through the chip. The chip has very precise flow conditions and this way we can very precisely and rapidly isolate those rare cells.
Kern: The CTC chip technology was initially developed with support from an NIBIB Quantum grant. They’re called quantum grants because the goal is to achieve a profound or quantum leap in healthcare. Toner says they’re making that leap:
Toner: We are developing a new technology that didn’t exist before. We are trying to understand the biology of these cells, because we know very little about these cells, and we are trying to identify and clinically validate applications, and that’s a pretty tall order, and it cannot be addressed by standard grant mechanisms. Quantum grants was the exact structure we were looking for.
Kern: Toner says the interdisciplinary nature of the project has been integral to its success, but also one of the most challenging aspects.
Toner: Our team has engineers, biologists and geneticists, and clinicians. The ability to pull a team like that together, getting everybody motivated, create the right incentives, and solve complex problems is really very difficult. I think that was the most difficult part, and it’s the part that requires a lot of attention, I call it social engineering. That’s the part that really fuels the entire enterprise
Kern: The beauty of the CTC chip says Toner is it wouldn’t place any additional burdens on the patient or physician.
Toner: It’s really taking the blood. We do that every day for millions of people. And instead of looking for X, Y, Z, now you’ll be looking for circulating tumor cells using this technology. So it really fits into the flow of physician-patient interaction very easily.
Kern: While not yet available clinically, nor a complete substitute for current cancer care, technology like Toner’s microfluidic CTC chip could someday make monitoring and treating cancer more manageable for clinicians and patients alike.
Toner: It will enable, in the long run, to treat the right patient with the right drug at right dose at the right time.
Kern: For NIBIB, I’m Margot Kern