A Multi-Analyte Blood Test for Cancer Detection and Localization

Cancer, usually referred to uncontrolled growth of abnormal cells, leading to the formation of a tumour. It is strongly believed that the best chance to arrest cancer is its early detection. Nevertheless, it is not possible to detect many tumors until it is grown sufficiently or it spreads across other parts of the body. Numerous efforts are constantly being made by several researchers to develop effective methods for cancer detection. During the uncontrolled growth of cancer cells some of them would die and shed their mutated DNA into the bloodstream. Liquid biopsy test could detect the DNA carrying mutations, which are associated with cancer. However, development of liquid biopsy test that is capable of screening healthy people remains a big challenge. In addition, the inability of the liquid biopsy test to detect the location of the cancer is a major limitation. A team of researchers at Johns Hopkins University School of Medicine, Baltimore led by Nickolas Papadopoulos and Bert Vogelstein have developed a multi-analyte blood test, referred as “CancerSEEK” for early detection of cancer. CancerSEEK is a ‘liquid biopsy test” that examines mutations in cell-free DNA and proteins circulating in the bloodstream (Fig. 1). This research work is funded by National Institute of Health (NIH), USA and the findings of this study is published recently in Science (J. D. Cohen et al., Science 10.1126/science.aar3247 (2018)).

Fig. 1 Schematic of the liquid biopsy test – Tumour cells shed protein and DNA into the blood stream that can be used as biomarkers for early cancer detection

About 1,005 patients diagnosed with ovary, liver, stomach, pancreas, esophagus, colorectum, lung, or breast cancers (Stage I to III) were used to check the ability of CancerSEEK in which none of them have received chemotherapy prior to blood sample collection and none had evident distant metastasis at the time of study. CancerSEEK evaluates the levels of 8 proteins and the presence of mutations in 2,001 genomic positions in 16 different genes, which helps to identify at least eight common types of cancers. Since the test uses a combination of protein biomarkers along with genetic biomarkers, a better sensitivity is achieved without compromising specificity. CancerSEEK is capable of not only identifying the presence of tumours but also localize the organ at which the cancer cells are grown.

CancerSEEK was found to be 98% accurate for tumours in ovary and liver. The median sensitivity of CancerSEEK was estimated to be 73% and 78% for stage II and stage III cancers, respectively. Unfortunately, the success rate of  CancerSEEK for stage I cancer was limited to 43% (Fig. 2(a)). In spite of its low detection ability for stage I cancer, its ability to narrow down the localization of the cancer in 83% of the patients (Fig. 2(b)) makes CancerSEEK as a most reliable method for cancer detection.

Fig. 2 Performance of CancerSEEK: (a) Sensitivity of CancerSEEK by stage; Bars represent the median sensitivity of the eight cancer types and error bars represent standard errors of the median; and (b) Sensitivity of CancerSEEK by tumor type. Error bars represent 95% confidence intervals.

CancerSEEK is expected to be available in the next few years at an estimated cost of less than US$500. Since cancer-related proteins used by Cancer-SEEK could also appear in people with inflammatory diseases such as arthritis, the applicability of this test for such patients is questioned. As an early detection is the key to surgically remove cancer cells before they metastasise, the detection level of 43% for stage I cancers needs to be improved by a large margin.

T.S.N. Sankara Narayanan

For more information, the reader may kindly refer to: J. D. Cohen et al., Science 10.1126/science.aar3247 (2018)

Non-Endoscopic Balloon-Based Device for Sampling Cancer Detection

Esophageal Adenocarcinoma (EAC) – the cancer that occurs in the lower portion of the esophagus (the food pipe that runs between throat and stomach) is the most common form of cancer in the United States. In spite of a steady increase in the incidence of EAC over the past 3 decades, the prognosis remains poor. Barrett’s esophagus (BE) is the only known precursor for EAC and it is currently diagnosed using an endoscope. Sanford Markowitz at Case Western Reserve University, Ohio, and his colleagues have demonstrated the feasibility of a non-endoscopic molecular cytology screening method for BE and EAC (Moinova et al., Science Translational Medicine, Vol. 10, Issue 424, eaao5848)

The non-endoscopic swallowable balloon-based esophageal sampling device consists of a pill-sized capsule (16 × 9 mm) attached to a thin 2.16 mm silicone catheter (Fig. 1, A and B), which can be easily swallowed. After delivery into the stomach, the balloon is inflated by injecting 5 cm³ of air through the catheter (Fig. 1C). The inflated balloon can be gently moved through the distal esophagus to collect samples from the luminal epithelial surface. Subsequently, the balloon is deflated and inverted back into the capsule (Fig. 1D). After complete retrieval of the capsule through the mouth, DNA is extracted from the balloon surface for molecular analysis. One of the prime advantages of this balloon-based sampling device is its ability to deploy rapidly by inflation unlike the conventional sponge-based devices, which requires sufficient waiting time for the coating to dissolve. The ability of the balloon to retract back into its capsule after sampling protects the sample from dilution or contamination from the proximal esophagus or oral cavity. The swallowable balloon-based device enables a simple and rapid method to collect DNA samples from the distal esophagus of unsedated outpatients. A combination of this balloon-based sampling device with bisulfite sequencing for detecting DNA methylation, provides a highly sensitive and specific yet minimally invasive screening protocol that could be clinically used for the detection and screening of BE.

Fig. 1 Non-endoscopic balloon-based device: (A) Device capsule and catheter (a vitamin pill and a dime are included for size comparison); (B) Capsule containing inverted balloon for swallowing; (C) Capsule with inflated balloon for esophageal sampling; and (D) Capsule containing inverted balloon for device and biospecimen retrieval.

T.S.N. Sankara Narayanan