Catching The First Drop Of Cancer

Emily BurkeCancer, Deoxyribonucleic Acid (DNA), Diagnostics, FDA, Monoclonal Antibodies, Ribonucleic Acid (RNA), Term of the Week, The WEEKLY

The Latest In Cancer Diagnostics

Hearing the words “it might be cancer” paired with your doctor’s perplexed look is enough to send shockwaves through your body. Getting to the heart of a diagnosis usually requires a surgical biopsy—removal and examination of the suspected tissue for visible signs of cancer.

Less invasive diagnostic tests—called liquid biopsies—might just bring more choices to doctors and patients. They are becoming today’s reality thanks to our ability to isolate molecules from body fluids. These diagnostic innovations pair technology with the latest in biomarkers—and will be coming to an oncologist near you.

Term Of The Week: Liquid Biopsy

Liquid biopsies provide information on the disease status of cancer in patients through the detection and analysis of biomarkers—think cell-free DNA, exosomes, circulating tumor cells—found in body liquids such as blood, urine, saliva and more.

Discovery By Cell-Free DNA

When cells in the body die, they release cell-free DNA (cfDNA)—this includes dying tumor cells. cfDNA-based tests are a type of liquid biopsy because they seek out biomarkers in body fluids and then identify cancer-specific mutations using PCR or next-generation sequencing analysis.

Trovagene (San Diego, CA) analyzes cfDNA found in urine samples, which patients collect at home. Currently, Trovagene has tests detecting mutations associated with melanoma, colon cancer, and non-small cell lung cancer, as well as the presence of viral DNA for the diagnosis of human papilloma virus.  Exact Sciences Laboratories (Madison, WI) uses at-home collection in their colon cancer test, which analyzes cfDNA in stool samples for cancer-associated DNA.

Genomic Health (Redwood City, CA) currently markets tissue-based genomic tests for the detection and classification of breast and prostate cancer, and is developing cfDNA-based tests for breast (blood sample) and bladder (urine sample) cancers.

Qiagen (Hilden, Germany) is developing cfDNA liquid biopsy diagnostics in partnership with pharmaceutical companies such as AstraZeneca (London, U.K.), Tokai Pharmaceuticals (Boston, MA), Novartis (Basel, Switzerland), and Eli Lilly (Indianapolis, IN).

Extracting Exosomes

Exosomes are lipid-encased vesicles that contain cellular protein, DNA, and RNA and typically have surface proteins specific to their native cell. These attributes, combined with the fact that they are found in many different body fluids, make exosomes a very attractive possibility for liquid biopsy. The idea is to capture exosomes based on tumor-specific surface markers or to collect exosomes and identify them as cancer-associated by examining the enclosed DNA or RNA.

Hot new startup Codiak BioSciences (Cambridge, MA) is looking at exosome-based pancreatic cancer diagnostics. Aptly named Exosome Diagnostics (Cambridge, MA) is in clinical testing of exosome-based urine and blood tests for prostate and lung cancer. Rounding out the pack is Qiagen, who is eyeing the possibility of exosome-based cancer diagnostics to compliment their work with cfDNA.

Consider Circulating Tumor Cells

The final category of liquid biopsy is perhaps the most obvious—circulating tumor cells (CTCs), or cells splintered from a tumor and circulating in the bloodstream. The challenge lies in detecting CTCs: some estimates classify them as rare as one circulating tumor cell per billion normal cells!

Janssen Diagnostics (Raritan, NJ) currently markets CellSearch, the single FDA-approved test that allows physicians to identify early CTCs from blood samples. 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, and a strong magnetic field is then applied to the sample, isolating the captured cells for identification and analysis. CellSearch is currently used to monitor the efficacy of treatments for breast, prostate, and colorectal cancer. 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.

Another way to identify CTCs 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. Although still in the preclinical research phase, this approach shows promise for capturing a wide range of CTCs.

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, 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.

Ultimately, the best liquid biopsies may contain a combination of all the above approaches. Biocept (San Diego) is leading the way by developing liquid biopsies that analyze both cfDNA and CTCs. Currently in the process of commercializing a breast cancer test, Biocept also has its eye on combination liquid biopsies for both colon cancer and melanoma.