New way to spot deadliest brain cancer

Dr Tang (far left) and Prof Ang at NNI's research lab. (Below) Glioblastoma cells as seen using a sophisticated technique called confocal microscopy, where the colours correspond to different proteins responsible for tumour spread.
Dr Tang (left) and Prof Ang at NNI's research lab.PHOTOS: CHEW SENG KIM, NNI NEURO-ONCOLOGY RESEARCH LABORATORY
Dr Tang (far left) and Prof Ang at NNI's research lab. (Below) Glioblastoma cells as seen using a sophisticated technique called confocal microscopy, where the colours correspond to different proteins responsible for tumour spread.
(Above) Glioblastoma cells as seen using a sophisticated technique called confocal microscopy, where the colours correspond to different proteins responsible for tumour spread.PHOTOS: CHEW SENG KIM, NNI NEURO-ONCOLOGY RESEARCH LABORATORY

Scientists identify 'signatures' of gene that makes tumour cells go berserk

Stepping into the laboratory of Associate Professor Ang Beng Ti and Dr Carol Tang at the National Neuroscience Institute (NNI) and negotiating the narrow "supermarket aisles" brimming with reagent bottles and experimental samples, one is spirited back to the kind of bedroom "chemistry lab" where inquisitive children plumbed the marvels of science.

Prof Ang and Dr Tang, both 46, lead a team of Singapore scientists who have found a powerful way to classify patients with glioblastoma, the deadliest kind of brain cancer.

They identified molecular "signatures" indicating the activity of a gene called ST3GAL1. This gene makes glioblastomas go berserk, often bringing death within two years of diagnosis, according to reports.

The discovery involved the lab mouse. Tumours extracted from humans were implanted in a "special type of mouse flown in from the US" that cost $300 each, said Dr Tang.

The immune response of this mouse could be suppressed to make it accept the tumours. Once in, the tumour retained its original molecular signature, but grew even faster and was much more accessible for study than in humans.

The team is the first in the world to employ this cutting-edge technique, said Prof Ang. It is a painstaking process, as the tumour cells have to be isolated and cultured in the test tube before implantation.

Molecular signatures are more reliable than previous methods in determining the type of tumour, and, even more importantly, potentially deciding which cancer drug to prescribe.

"The focus is no longer on how tumours look under the microscope," said Prof Ang, as similar-looking tumours may behave very differently.

This new approach might spare the patient from the debilitating side effects of the customary regime of radiotherapy and chemotherapy. It is an example of the so-called precision medicine, hailed as "a bold new research effort" by the White House last year.

It may take years, however, for "precision" drugs to be found and certified for ST3GAL1. Such targeted therapy "would probably be at least a decade in the making", said Dr Wong Seng Weng, medical director of The Cancer Centre, a subsidiary of specialised healthcare provider Singapore Medical Group. "Targeting a cancer-related pathway can sometimes have huge repercussions on normal cellular functions, leading to significant side effects."

A 2015 Time magazine report strikes a cautious note as well, saying that although an experimental drug has had positive effects on one glioblastoma patient, it remains a challenge to find the right drug for each individual.

The journey of the Singapore team has been arduous.

The quest took seven years and a collaboration among six institutions - NNI, National University of Singapore, the Agency for Science, Technology and Research, Nanyang Technological University, National Cancer Centre and Duke-NUS Graduate Medical School.

When their research paper was completed, Dr Tang said "it went back and forth for another year and a half" among the researchers, peer reviewers and editors before it was accepted by the prestigious Journal Of The National Cancer Institute in the United States. The protracted review process attests to the novelty of their discoveries.

One of the two principal authors, Dr Chong Yuk Kien, 33, got his PhD in the course of the project, while Mr Edwin Sandanaraj, 38, is in his first year of doctoral studies. And so the spirit lives on, of the "tenacity and perseverance" that Dr Tang said are "critical for groundbreaking research that runs over years".

A version of this article appeared in the print edition of The Straits Times on January 08, 2016, with the headline 'New way to spot deadliest brain cancer'. Print Edition | Subscribe