From OncoLog, March 2011, Vol. 56, No. 3
MD Anderson One of Four Centers to Test Cancer Cell Detection Chip
By Joe Munch
A new test that could monitor the effectiveness of cancer treatment by capturing circulating tumor cells from patients’ blood samples, allowing the cells to be quantified and analyzed, is scheduled to begin clinical testing at MD Anderson and other institutions this year.
The test, which can detect 1 cancer cell among 1 billion healthy cells, is being developed at Massachusetts General Hospital in Boston.
An early version of the test used a microchip, called a CTC-Chip, which resembled a glass microscope slide with tiny posts that captured circulating tumor cells as blood was forced through the chip. The posts were coated with antibodies that would bind to tumor cells but not to normal blood cells. Stains then allowed researchers to count and capture the cells for analysis. The second-generation chip, called the HB-Chip, uses a herringbone design instead of posts to capture tumor cells and will be tested in clinical studies at MD Anderson and three other centers this year.
At MD Anderson, the HB-Chip will be used to capture circulating tumor cells in blood from patients in a number of settings, including the Biomarker-integrated Approaches to Targeted Therapy for Lung Cancer Elimination (BATTLE) II trial. Like the first BATTLE trial, whose results were reported in the June 2010 issue of OncoLog, BATTLE II will study four different chemotherapy regimens in patients with advanced, treatment-refractory lung cancer. Patient enrollment for BATTLE II is expected to begin soon.
“The number of circulating tumor cells could be a measure of the effectiveness of therapy,” said Roy S. Herbst, M.D., Ph.D., chief of the Section of Thoracic Medical Oncology and a professor in the Department of Thoracic/Head and Neck Medical Oncology at MD Anderson. “In addition to quantifying the circulating tumor cells, our team wants to analyze these cells for genetic mutations, gene amplification, and expression of proteins—what many would call a liquid biopsy.”
For patients in the BATTLE II trial, blood samples will be drawn on the same day tumor specimens are obtained by core needle biopsy, before the patients begin treatment. The characteristics of the circulating tumor cells captured with the HB-Chip from the blood samples will be compared to those of the biopsy specimens; as part of the trial protocol, researchers will check both groups of tumor cells for biomarkers associated with effectiveness of therapy. The principal investigator of this trial is Vali Papadimitrakopoulou, M.D., a professor in the Department of Thoracic/Head and Neck Medical Oncology.
Researchers will also look at pharmacodynamic markers in circulating tumor cells obtained during and after treatment. Dr. Herbst said these analyses may help researchers better understand how cells respond to treatment and why some cells are resistant to therapy.
“The beauty of doing these tests at MD Anderson is that the large population of patients participating in clinical studies allows us to incorporate the blood tests into other clinical trial protocols,” Dr. Herbst said. He added that it might be possible to test the HB-Chip in conjunction with upcoming clinical trials for the treatment of prostate, gastrointestinal, and breast cancers at MD Anderson.
The only blood test for circulating tumor cells currently on the market is CellSearch, made by Veridex, a Johnson & Johnson subsidiary. CellSearch detects circulating tumor cells but does not capture them intact. Because capturing the cells whole allows them to be analyzed like biopsy specimens, there is hope that the HB-Chip or one of its successors might also have predictive value or even eliminate the need for a needle biopsy in some patients in whom metastatic cancer is suspected. However, Dr. Herbst said he expects the main clinical use of the HB-Chip initially will be measuring a patient’s response to therapy.
Several studies have found that circulating tumor cells are associated with poor prognosis in patients with various cancers, and it is believed that circulating tumor cells are an indicator of metastatic disease. However, the exact nature of the relationship between circulating cells and metastatic disease is not known. “Not all circulating tumor cells may have the ability to invade,” Dr. Herbst said. “This is one of the things we hope to learn.”
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