Two scientists at the National Neuroscience Institute (NNI) in Singapore appear to have yanked open a new flank in the battle against Glioblastoma, a swift and deadly form of brain cancer that kills most of its victims within 18 months of diagnosis despite surgery and chemotherapy. Only last week, a 29-year-old US woman decided to opt for euthanasia and end her life on her own terms after a grim and excruciatingly painful struggle against brain cancer.
The scientists in Singapore may have spotted a chink in the deadly and seemingly impregnable armour of this disease based on their study of genetic information contained in surgically removed tumours. Over the last decade these scientists had compiled a database of such tumours and their bank now contains about a 100 samples.
As part of their path-breaking work senior research scientist Carol Tang and Associate Professor Christopher Ang, have discovered how to reproduce the tumour cells and implant them in mice so that they will grow exactly as they would in humans. This is a breakthrough as reproduced versions and cells bought commercially are in an altered state and do not reflect what happened in human patients when implanted in mice.
Pharmaceutical companies can now use the mice carrying tumour implants developed by the scientists in Singapore to test experimental drugs and fine-tune their clinical drug trials so only patients with tumours that could respond take part.
“More and superior cancer drugs will make it to the market as this will improve the trial results,” said NNI’s Dr Ang. “Such an approach driven by genetics rather than observation is long overdue.” At present doctors remove a cancer and decide on its type and treatment based on a microscopic study of its features, called histology.” However, latest research in the US has shown that tumours that look the same may not be the same and the crucial differences among them can be confirmed only by looking at their molecular biology. It is because of these below-the-surface differences that some patients respond to a drug while others do not, even if their tumours look alike under the microscope.
“If a patient doesn’t respond, then random mixtures of another set of chemotherapy drugs are tried out without still knowing whether he will respond,” he said. “Usually, the patient is so ill by the second trial that he succumbs to the disease, so the window for treatment is quite short.” In September, a group of 27 neuroscientists from around the world came to the same conclusions as the NNI scientists.
Dr Tang believes the NNI’s research could eventually lead to patients getting a more personalized diagnosis within days of surgery and consequently more effective drugs. Usually, by genetic profiling doctors refer to the time-consuming process of looking at up to 800 gene signatures to see if the drugs will work. “That could take four to five months, too much time and cost to be useful for the patient.” NNI on the other hand, will build on US researchers’ work in mapping somatic mutations, or changes in a person’s DNA that occur after birth. A fairly comprehensive database of such mutations already exists. The idea is to establish a link between the various tumour types and somatic mutation patterns, and the effectiveness of drugs against the tumours.