Cancer cells may guide treatment
Changes in patient monitored in lab
A Boston-based team published proof Thursday that one of the most alluring ideas in cancer care can work: Exceedingly rare tumor cells can be filtered from a patient’s blood sample and used to noninvasively monitor the evolution of cancer and identify the most promising treatments.
The scientists drew blood from women with one type of breast cancer, isolated the rare cancer cells, and then experimented with those cells in a laboratory dish to find drugs that might effectively halt the spreading cancer.
The work demonstrates a powerful way to track and personalize cancer treatment with a simple blood draw. The technique, described in the journal Science, could enable doctors to frequently check for genetic changes that allow tumors to develop resistance to medications and to fine-tune therapy.
“Tumors change, and from the time that a woman is diagnosed with metastatic breast cancer that needs to be treated to the time that multiple treatments have worked and stop working, the tumors have evolved,” said Dr. Daniel Haber, director of the Massachusetts General Hospital Cancer Center and oversaw the study. The new technique would allow “real time monitoring’’ of these changes without having to perform invasive biopsies, he said.
The next steps are to improve the technique, which worked in only a fraction of the patients tried, and to test whether giving patients personalized drug regimens identified with the method will halt their tumors’ growth and prolong their lives. Independent researchers said the technique would need to be made more efficient, reliable, and faster before it could be widely used. It also remains to be seen how difficult it will be to grow cells for other types of cancer.
Circulating tumor cells, which are thought to be responsible for seeding cancer’s spread beyond the initial tumor, were discovered 150 years ago. Thus far, they have mainly been used to predict whether a cancer was likely to get worse or not.
Early efforts to use that information to change treatment have had disappointing results. A paper published in the Journal of Clinical Oncology last month reported that breast cancer patients who were tested for circulating tumor cells and then switched to a different chemotherapy when there were signs their current therapy was not working did not survive longer or had slowed tumor growth compared with patients who remained on the regular treatment.
That work was co-authored by Dr. Daniel Hayes, clinical director of the breast oncology program at the University of Michigan Comprehensive Cancer Center, who said he was “very jealous” of the team behind the new study.
“Dr. Haber has beaten us to the punch — and that is can you grow these cells in culture and use them as an indicator for that patient, whether she’s going to respond to a certain therapy or not. They didn’t prove that by any means, but that’s the promise of this paper,” Hayes said.
Researchers at Mass. General partnered with Johnson & Johnson on the research to develop the chip used to filter out and isolate the circulating tumor cells, called the CTC-iChip.
Improvements in the chip contributed to the success of the new experiment. An earlier generation of the technology filtered out circulating tumor cells, but had limitations. It could nab only certain cancer cells, and it was difficult to remove the cells from the filtration device and get them to grow in a dish.
The new technology is a kind of miniature racing circuit for blood; It is the size of a microscope slide, with tiny channels carved into it. Cells are sorted first by size, eliminating the small red blood cells. Then, researchers add a magnetic coating that homes to white blood cells and use magnets to select out the tumor cells needed for testing. These cells could then be used to grow tumors in mice and lab dishes,
By taking repeated samples from women, the researchers were able to measure the emergence of new mutations that were not present in the initial tumor, and may signal the need to change treatment. They tested the effectiveness of various drugs by seeing whether they could inhibit the growth of tumor cells in the dishes and the mice, suggesting the technique could provide a way to personalize a drug regimen to an individual’s cancer.
The process, however, is far from efficient — a challenge that researchers are now focused on improving. In the study, only six out of 36 samples with a particular type of breast cancer could be successfully grown in a dish.
“Scientifically, it is an important paper,” said Dr. Massimo Cristofanilli, deputy director of translational research at Thomas Jefferson University’s Kimmel Cancer Center, who was not involved in the study. “It’s exciting to see we can use circulating tumor cells for a variety of analyses; we can even culture these cells — we can certainly understand the biology of these cells.” But he added that the applicability to patient care was not clear because the process of growing the tumor cells was successful in only some of the cases, took months, and would probably be expensive.
Zena Werb, a professor of anatomy at the University of California, San Francisco, who was not involved in the work, said that the researchers’ success in getting cells to grow in a dish and to create tumors in mice is surprising and exciting, if it can be repeated.
“That means it’s possible to try to do some personalized medicine, in terms of the mutations that these individuals had, to see if there are specific treatments” that might work better, Werb said.