This breast cancer circulating tumor cell culture was isolated from a patient’s blood sample using the CTC-iChip and expanded in the laboratory for drug testing. Researchers at the Massachusetts General Hospital Cancer Center at Harvard Medical School and the Harvard Center for Bioengineering in Medicine are developing the CTC-iChip through a collaboration funded partly funded by Janssen Diagnostics.(Courtesy of Min Yu, PhD, MD/Newswise)
At least 30 companies are seeking to develop the next generation of circulating tumor cell (CTC) technology, part of an emerging focus on analyzing the biofluids of patients with cancer as a “liquid biopsy,” particularly for solid tumors.
Fueled in part by the National Cancer Institute, the research efforts concentrate on creating methods of extracting CTCs from blood samples so that they can be analyzed on a molecular level.1
Thus far, the CellSearch system is the only in vitro CTC diagnostic to gain the FDA’s approval, although other assays are available commercially as laboratory developed tests. Initially approved in 2004, CellSearch is indicated for detecting the presence of CTCs and monitoring disease progression through CTC levels in patients with metastatic breast, colorectal, and prostate cancer.
Although the enumeration of CTCs has demonstrated analytical and clinical validity in these tumor types, the CellSearch test has not yet been established as a means of selecting therapies for these patient populations, hampering its incorporation into treatment guidelines. Medicare covers CTC testing, but the reimbursement picture in the private insurance industry is spotty.
Janssen Diagnostics, which owns the CellSearch technology, is actively seeking to validate its clinical utility through large studies in the United States and Europe. In addition, Janssen is developing the CTC-iChip, which isolates CTCs suitable for both standard clinical diagnostic cytopathology and advanced genetic and molecular analysis, through a collaboration with researchers at the Massachusetts General Hospital Cancer Center.
Similarly, major pharmaceutical companies and emerging biotechnology firms have partnered with each other and with academic institutions to develop CTC technology.
“These companies are not all ‘me too’ companies trying to just harvest the cells,” Enal Razvi, PhD, managing director of Select Biosciences US, a market research and life sciences conference company, said in an interview. “That's been done. Now, the challenge is to go to the next level—capture the cells and then ask the question: What do these cells do in the body, what is their potential to metastasize, and are they truly going to seed a new tumor? That’s the belief, but the proof remains.
“Just counting the number of cells gives you very basic information. It doesn't provide you with the details and that’s been a challenge of CTCs,” added Razvi. “For CTCs to have their full impact in the clinic, you need to have more depth and that depth comes from a molecular analysis of these tumor cells that had been harvested from the patient.”The Competitive Landscape
Razvi said about 30 companies are working on CTC technology. He values the current market for CTC diagnostics at $200 million to $250 million annually, with most of the testing being performed in the United States. That market, however, is likely to expand internationally.
“China, for example, is embracing a lot of this work with biofluid biopsies and, in in fact, Chinese companies are offering these CTC tests, so the market number is surely going to increase and grow,” said Razvi.
Indeed, Biocept Inc, a molecular diagnostics company based in San Diego, California, announced in September that the company has obtained a patent in China for its microfluidic technology that captures CTCs.2
In the United States, the company is collaborating with The University of Texas MD Anderson Cancer Center to study its OncoCEE device for evaluating HER3 expression in ovarian cancer CTCs.3
Biocept has launched an OncoCEE test for breast cancer and plans to introduce tests for lung, colorectal, prostate, and other solid tumors.3
Biocept was among 10 companies that respondents to an industry survey cited as those whose technologies hold the most promise for improving the ability to study and measure CTCs. 4
Janssen Diagnostics led the field by a wide margin, according to the survey, conducted last year as part of the Circulate: Circulating Cancer Biomarkers conference held in Boston. Also making the list were Fluidigm, Fluxion, Miltenyi Biotec’s MACS system, ScreenCell, Advanced Cell Diagnostics, CytoTrack, BioFluidica, and SRI Biosciences’ FASTcell system.
Other companies whose technology has attracted attention in research circles include Epic Sciences and Cynvenio Biosystems.