Novel Noninvasive Diagnostic Test Developed for Colorectal Cancer

Researchers have developed a genetic test for colorectal cancer (CRC) using a novel liquid “biopsy” of circulating tumor cells (CTCs) from whole blood, a rapid, easy-to-use technology developed to improve treatment, monitoring, and overall care of cancer patients.

The CTC liquid biopsy and CRC genetic test were developed by researchers from the Institute of Bioengineering and Nanotechnology (IBN; Singapore) of Singapore’s Agency for Science, Technology and Research (A*STAR). The standard approach tests surgically removed tissue for genotyping. If the cancer has metastasized, additional samples are removed, which comes with additional pain, inconvenience, risk of acquired infection, and financial costs. In contrast, IBN’s liquid biopsy enables testing blood samples, offering a relatively non-invasive alternative.

“We are excited about our liquid biopsy approach, which could make it easier for doctors to check and administer the appropriate drug treatment for cancer patients. Our technologies have been validated by Fortis Surgical Hospital and have been successfully licensed for clinical applications,” said Prof. Jackie Y. Ying, executive director, IBN.

CTCs provide early indication of metastasis, but are extremely rare. IBN researchers fabricated a silicon microsieve to rapidly capture and enrich CTCs from blood. Measuring 7.5 mm in diameter, the microsieve utilizes a densely packed array of 90,000 fine pores to separate CTCs (generally larger and stiffer) from normal blood cells, within 5 minutes. IBN’s microsieve can be used for rapid detection and clinical analysis of CTCs and for metastasis research.

CRC is known to have two key mutated genes, KRAS and BRAF. IBN researchers developed ultrasensitive molecular assays to identify mutations using the CTCs. The assays, tested on 44 CRC surgery patients, were highly accurate in detecting KRAS and BRAF mutations, a major milestone of the Fortis-IBN TissueBank, established to advance translational research in colorectal care.

Dr. Min-Han Tan, IBN team leader and principal research scientist, said: “Our work shows matching genetic mutations in the tumor tissue and corresponding CTCs of patients with CRC. This opens up an avenue for liquid biopsies, or the testing of cancer cells through blood, which we hope can reduce the need for invasive biopsies.”

The noninvasive genetic test was recently licensed to AITbiotech Pte Ltd. (Singapore) for development into a ready-to-use kit. “We are pleased to be IBN’s commercialization partner for these test kits. This is a good example of a win-win public-private partnership, whereby a local SME like us is able to leverage on IBN’s expertise,” said AITbiotech CEO Alex Thian. The microsieve technology was licensed in 2011 to CellSievo Pte Ltd (of IBN) for commercialization.

Dr. Poh-Koon Koh, senior consultant and director, Colorectal Surgical Oncology & Cancer Genetics Service, Fortis Surgical Hospital, and IBN adjunct clinician scientist, said: “In partnering IBN to set up the Fortis-IBN TissueBank, our aim was to create a resource that will allow cutting-edge research to benefit patients clinically. This liquid biopsy invention is an invaluable tool [and] allows a noninvasive means to obtain DNA material in tumors that are not easily or safely accessible through conventional biopsy techniques.”

The noninvasive genetic test for colorectal cancer was reported by Mohd Suhaimi NA et al., online January 2015, in the journal Molecular Oncology. The microsieve capture of CTCs from whole blood was reported by Lim LS et al., online August 2012, in the journal Lab on a chip.

Related Links:
Institute of Bioengineering and Nanotechnology
Agency for Science, Technology and Research (A*STAR)