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Singapore doctors make vital discovery on child cancer

TAIPEI, Taiwan -- Doctors in Singapore have uncovered a genetic key which unlocks the survival chances of childhood leukemia patients.

In doing so, they can tailor more effective treatments for those who currently have a poor prognosis.

“This is important because we can potentially use this information to identify patients who do badly right at the beginning of treatment and who may benefit from a different treatment approach,” said Associate Professor Chng Wee Joo, head of the division of hematology at the National University Cancer Institute Singapore and deputy director of the Cancer Science Institute of Singapore.

Even better: There are already cancer drugs being tested in clinical trials that could reverse this drug resistance, so patients will not have to wait as long to try out the new drugs.

The disease under the microscope — acute lymphoblastic leukaemia (ALL) — is the most common childhood cancer, affecting about 30 to 40 children here each year.

Although about nine in 10 patients are cured, the remaining 10 percent have not fared well because they are resistant to chemotherapy drugs.

The team from the National University Health System identified the gene — microRNA 335 — which is expressed in much lower levels in patients with a poor prognosis. It controls other chemical reactions, which then affect whether patients will benefit from prednisolone — a key chemotherapy drug.

MicroRNAs are small non-protein coding genes present in animals and plants, and they represent about 4 percent of the genes in the human genome.

These tiny pieces of genetic material play an important role in controlling how genes function, and there is growing evidence that they play crucial roles in cancer, and how patients respond to specific treatments.

The work, by doctors from the National University Hospital and the cancer institute, compared the patients who were cured with those who did not do well, to sieve out genes that were expressed differently and could be affecting the outcome.

The work hinged on blood and bone marrow samples taken from patients.

Said Associate Professor Allen Yeoh, senior consultant at National University Hospital's pediatric haematology-oncology division: “Current technology is both expensive and toxic, so we need to balance treatments so we can treat aggressively enough to kill the cancer cells while minimising harm to normal cells and the long-term side effects.

“We believe we are looking at the Achilles' heel of this disease, and for patients with really poor outcome, we hope to soon use the new drugs targeting the mechanism of drug resistance caused by microRNA 335, in addition to regular chemotherapy.”

The next step is to do further tests, and to see if the same results happen in adult patients with the same cancer, who tend to fare worse than children.

Researchers here have made several significant breakthroughs in treating ALL, which was once a death sentence for children.

In an earlier study, for instance, they were able to single out patients who benefited from three drugs instead of the conventional four used in chemotherapy in the first month after diagnosis. This means fewer side-effects such as ulcers, fever and infection.

The nine in 10 patients able to skip the most toxic fourth drug stayed in hospital only a week, compared to the usual one month.

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