Dr. Mehmet Toner and Dr. Daniel Haber
Two years ago, a team of scientists at theMassachusetts General Hospital Cancer Centertook the cancer research community by storm. Led by Mehmet Toner, PhD, director of the Center for BioMicroElectroMechanical Systems (BioMEMS) and Daniel Haber, MD, PhD, director of the Cancer Center, the team published two papers, the first in Nature and the second in the New England Journal of Medicine, demonstrating promising results for a new nanotechnology device: The CTC-chip.
A silicon chamber containing thousands of microscopic columns through which is passed a teaspoon of blood, the CTC-chip allows the capture of rare cancer cells that circulate in the blood of patients with invasive cancers. Once captured, these extraordinarily rare cancer cells can be analyzed to reveal critical information about the spread of cancer metastases and the potential effectiveness of different treatments. This approach offers the potential to revolutionize the way oncologists detect, monitor and treat cancers in the future.
Stand Up to Cancer Challenge
Inspired by these promising early results and the Stand Up to Cancer (SU2C) initiative to “move groundbreaking cancer research out of the lab and into the clinic,” Haber and Toner assembled a cancer research “Dream Team.” Promoted on national television with a roster of A-list celebrities, including movie stars, recording artists and national news anchors, SU2C’s bold new paradigm for funding cancer research uses a model that requires applicants to reach across disciplines and institutions to create unparalleled scientific collaborations in an effort to accelerate clinical discoveries.
“The most exciting thing about the SU2C challenge,” says Haber, “is that it encourages collaboration. It comes from the idea that we really can make progress if creative groups from different disciplines work together.”
The Making of a Dream Team
Within Mass General, the Dream Team includes bioengineers, molecular biologists and clinicians, who have worked together to make the CTC-chip a reality. The Mass General team reached out to partners at multiple institutions to further accelerate research: Bioengineers at MIT will work with Mass General engineers to enhance the CTC-chip technology for even greater sensitivity. Clinical researchers at Mass General, Memorial Sloan-Kettering Cancer Center, Dana-Farber Cancer Institute and M.D. Anderson Cancer Center will work together to define applications for the CTC-chip for many different types of cancer.
This May, a blue ribbon scientific advisory committee commissioned by SU2C’s scientific partner, the American Association of Cancer Research, awarded the Cancer Center $15 million to fund the CTC-chip Dream Team. The proposal was one of five chosen nationally from among 237 submissions, by a prestigious review committee led by Nobel laureate Phil Sharp, PhD, and comprised of prominent scientists and clinicians.
Toner credits the unique environment at Mass General for their success. “Mass General has all three components required for major clinical breakthroughs,” he says, listing technology, molecular and biological sciences and clinical medicine as the fundamental elements. “All of these components are under the umbrella of the same organization. There are few places in the world that can do this as effectively.”
Bringing Together Research, Clinical Medicine and Technology
Circulating tumor cell captured on microfluidic posts, as seen by a scanning electron microscope
The star of this project, the CTC-chip, is about the size of a business card and holds 80,000 microscopic posts coated with an antibody that attracts tumor cells circulating in the blood. These living cancer cells, which cling to the posts, can then be analyzed.
Although the existence of circulating tumor cells (CTCs) has been known for roughly 140 years, they have eluded researchers because they are so rare—as few as 10 may be lurking in one milliliter of blood containing about eight billion normal cells—and because there has not been technology sensitive enough to efficiently capture them—until now.
“The big hope is that we may be able to find the cancer cells that are capable of spreading from the primary tumor to distant sites,” says Haber. “This would allow physicians to detect invasive cancers early, follow how well cancers are responding to treatments in ‘real time’ and possibly even develop new drugs that are specifically aimed at suppressing these metastasizing cancer cells.”
In clinical studies conducted over the past two years, the CTC-chip was used to identify circulating cancer cells in the blood of patients with metastatic cancers of the prostate, lung, pancreas, colon and breast. In some patients with lung cancer, where targeted “smart drugs” can focus on the genetic lesions causing the cancer to grow, the CTC-chip can identify that genetic lesion and help identify which patient is likely to benefit from these novel drugs.
In the future, the CTC-chip may reduce the need for repeated biopsies or imaging studies.
"Going through chemotherapy is very difficult, but the biopsies for my prostate cancer were even more painful,” says John Shea, one of the participants in the CTC-chip clinical trial. "Now every time I come in they take a blood sample."
“As our cancer treatments become better and more focused on different types of gene abnormalities within each cancer, it will become absolutely essential to know what you are treating when you are treating it,” says Haber. He hopes the CTC-chip will one day make cancer treatments more like the treatment of infectious diseases, where drug sensitivity patterns can be predicted before antivirals or antibiotics are prescribed.
Moving Toward the Next PhaseAlthough the CTC-chip has made a stunning debut, Haber stresses that currently, this technology is still in very early stages and it is still “very much a test in development.”
“The study of CTCs is in its infancy, both in terms of technology and in terms of understanding the clinical implications of what we find with that technology. There is no gold standard yet that tells us what type of information will be clinically useful and what information needs much more analysis before it can be applied,” he continues. “Right now, we aren’t ready for clinical use, and much more research needs to be done.”
And yet, he is hopeful: “It’s very humbling for all of us on the Dream Team to work on a project that is so much bigger than any of us. Whatever impact this technology turns out to have in the end, this is the most exciting research that any of us have ever done.”
Although the CTC-chip technology is not yet ready for widespread use in clinical settings, with the support of the SU2C grant and the work of the Dream Team, this new technology may one day become a reality for cancer patients.
Through a powerful synergy between scientists in the laboratories and physicians at the bedside, the Mass General Cancer Center fosters innovation in basic, translational and clinical research. Learn more about current research underway at the Cancer Center.