Breaking from the Pack with Cancer Diagnostics

Regular WEEKLY readers know cancer stems from the division of a single cell leaping to uncontrolled growth and then growing into a tumor. So, how exactly does cancer disrupt the life process? Sometimes tumors grow to such a size the function of a vital organ is no longer viable. But mostly cancer kills by metastasis: when cells from the tumor break away and spread to other unrelated tissues.

Circulating tumor cells (CTCs), or cells splintered from a tumor and circulating in the bloodstream, reveal one of the earliest signs of metastasis. These renegade cells are the running backs of cancer – detecting these cells early can lead to quicker diagnosis. Monitoring these cells can result in tracking changes over time without repeated invasive biopsies and highlights the diagnostic power of CTCs ability to assess the effectiveness of various therapies in real time.

The challenge lies in detecting CTCs; some estimates classify them as rare as one circulating tumor cell per billion normal cells! With only one CTC diagnostic currently on the market, the game is on for other companies to bring their players to the field.

THE SEARCH IS ON

Janssen Diagnostics (Raritan, NJ) currently markets CellSearch, the single FDA approved test that allows physicians to identify early CTCs from blood samples.

How does CellSearch work? Monoclonal antibodies (mAbs), capable of recognizing proteins on the surface of migrating tumor cells, are chemically linked to magnetic nanoparticles and then added to a patient’s blood sample. These tumor-specific mAbs grab hold of the CTCs – a strong magnetic field is then applied to the sample, isolating the captured cells for identification and analysis.

A higher number of CTCs detected may indicate a higher incidence of metastasis, or a less than effective treatment route if used to quantify cancer therapy success. CellSearch keeps tabs on CTC cell counts for breast, prostate, and colorectal cancers.

CASTING A WIDER NET

One criticism of using a mAb-based approach to isolating CTCs: it forces the researcher to limit the specific cell-surface protein markers they choose to focus on during the isolation process. All CTCs do not carry the same markers and many haven’t even been identified, so finding a more universal marker is a top priority. One such marker may be cell size – CTCs tend to be significantly larger than other cells in the blood, and this size differential may be exploited in a microfluidics-based approach to cell separation.

Researchers at National University in Singapore (Singapore) and MIT (Cambridge, MA) have developed a microfluidics chip that routes cells from a blood sample into different channels based upon cell size. The larger CTCs directed into the appropriate channel are easily collected for further analysis. While still in the preclinical research phase, this approach shows promise for capturing a wide range of CTCs.

COCKTAIL FODDER

CTCs aren’t new to the game of diagnostics, we’ve known about them since 1869 – when pathologist Thomas Ashworth observed them in the blood of a cancer patient. Researchers finally honed in on the technology in the mid-1990s and CellSearch was granted FDA approval in 2004.

NO CELL LEFT BEHIND

Epic Sciences (San Diego, CA) adopts a “no cell left behind” game plan thanks to technology developed by the Scripps Research Institute (La Jolla, CA).

Automated fluorescence-microscopy identifies the CTCs in blood samples placed on microscope slides. A detailed analysis of three million cells per slide is performed – with each blood sample yielding approximately twelve slides. This technology may potentially hone in on the presence of a single CTC.

Epic Sciences currently uses their test to perform analyses for biotech, pharmaceutical, and clinical research partners, with a long term goal of releasing a diagnostic product for reference labs.