Cancer scientists’ brainwave
Scientists in Singapore have opened a new frontier in the fight against glioblastoma, a swift and deadly form of brain cancer.
Spreading quietly in the brain, the disease usually announces itself in the form of fits and seizures in the patient, or headaches due to the tumour expanding and exerting pressure on the skull.
While the cancer is much rarer than, say, breast and lung cancer, it is deadlier, killing most patients within 18 months even if they have surgery and chemotherapy.
In Singapore, there were 1,903 cases of brain cancer between 1968 and 2007.
In a stark reminder of patients’ grim prospects, a 29-year-old US woman was in the headlines globally last weekend for ending her life by doctor-assisted suicide, as she wanted to die on her own terms.
To help people like her, two scientists from the National Neuroscience Institute (NNI) in Singapore have been compiling a database of tumours removed from patients here during surgery.
Over the past decade, they have been storing the physical samples and looking into the tumours’ genetic information, which could shed light on their weaknesses.
The brain tumour bank comprises about 100 samples.
Senior research scientist Carol Tang and Associate Professor Christopher Ang, head of neurosurgery at NNI’s Singapore General Hospital campus, have also developed a way to reproduce the tumour cells and implant them in mice so that they will grow exactly as they grew in the patients.
This is a breakthrough as scientists traditionally have only a finite supply of cells from the original, excised tumours for research and tests. Reproduced versions and cells bought commercially are usually altered and, when implanted in mice, do not reflect what happened in patients.
Pharmaceutical companies can also use the mice to test experimental drugs, and use the results to fine-tune their clinical drug trials so only patients with tumours that could respond take part in the trials.
“This will improve the trial results so more cancer drugs make it to the market,” said NNI’s Dr Ang.
The institute has been working with American drug company Eli Lilly on anti-brain cancer drugs.
Dr Tang said such a genetics- driven approach to diagnosing and treating brain tumours is long overdue.
Currently, most doctors still rely on observation to identify the tumour type and decide on the treatment.
After surgery to remove the tumour, they usually put a sample under the microscope to identify what type it is through its features.
“But this method, called histology, is very subjective, and if the tumour is not the same throughout, some features may be missed,” she said.
Research in the United States has shown that tumours that look the same may not be the same. It is only by looking at their molecular biology that scientists can detect differences, she added.
There are more than 100 types of brain tumours, according to charity Cancer Research UK.
Such below-the-surface differences could explain why some patients respond to a drug while others do not, even if their tumours look alike under the microscope.
The standard treatment for glioblastomas now is surgery followed by radiation and chemotherapy, said Dr Ang.
“If the patient doesn’t respond, then you try random mixtures of another set of chemotherapy drugs, but you still won’t know if the patient 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.
The international scientists at a meeting in the Netherlands sponsored by the International Society of Neuropathologists, discussed major discoveries in the biology of central nervous system tumours, which include brain tumours.
The group recommended that the World Health Organisation take into account the tumours’ genetic differences when it revises its classification. The last revision was in 2007 and there is no specified date for the next one.
The scientists noted that research in the past decade had significantly improved the biological understanding of the molecular basis of human tumours.
“Brain tumours have shared in this molecular revolution, and in some areas have been at the forefront,” they said in a paper. “Such information can have diagnostic, prognostic and predictive value.”
Dr Tang believes the NNI’s research could eventually lead to patients getting a more personalised diagnosis within days of surgery, so that the most effective drugs can be prescribed.
Usually, when doctors talk about genetic profiling, that involves 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,” she said.
Instead, the NNI 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.
Dr Tang said: “In the future, we should be able to just test which somatic mutations a patient has.
“That could take as little as a day, compared to months for the gene signatures. Then we can guess which drugs will be useful for the patient, and hopefully get them better.”
Source: Asia One
Published: 11 Nov 2014
