Gene makes cancer drugs less effective for Asians

SINGAPORE - Singapore researchers have uncovered why a group of drugs that works well on certain lung and blood cancers does poorly on some patients here, and hope to soon start trials for a new treatment.

The culprit: a gene variation which shows up in about 15 per cent of East Asians but does not surface at all in Caucasians and Africans.

The problem can potentially be overcome by adding another drug to the mix.

This has worked in the test tube and researchers hope to test the new treatment on patients here in one to two years.

"We were able to figure out how the gene variant caused resistance to the cancer drug, and then found another drug to restore the ability to kill cancer cells," said Associate Professor Ong Sin Tiong of the Cancer and Stem Cell Biology Signature Research Programme at Duke-NUS Graduate Medical School, one of two lead investigators in the study.

The other was Dr Ruan Yijun, then at the Genome Institute of Singapore.

This work is of particular relevance here since the mutation is found exclusively in East Asians.

"The drugs used to target these cancers are very expensive, costing thousands of dollars a month, and we want to know from the get-go, before starting treatment, if they are less likely to work, and then decide if there are any strategies to help them work better," said Prof Ong.

"All it takes is a simple test on a small tissue sample, such as blood or saliva, to test for the gene variant, and this is a terrific advantage when the cancer is in a difficult place to reach such as in the lungs."

It is good news for the estimated 14,000 people worldwide with the mutated gene who are diagnosed with such cancers each year.

First to benefit will be Singapore patients because the clinical trial will likely be done here, said Dr Charles Chuah, senior consultant at the Singapore General Hospital's Haematology Department and another researcher in the study.

"The results wouldn't have been possible without involving scientists and clinicians who worked so well together," he added.

More than 50 researchers took part in the massive effort, including those from the Duke-NUS Graduate Medical School, Genome Institute of Singapore, SGH and the National Cancer Centre Singapore.

Human Genome Organisation (Hugo) president Edison Liu pointed out how the current "genomics revolution" was transforming the course of medicine.

"This work is an example where sequencing uncovered a genetic cause for resistance to a drug, that when applied to a population, is now part of a drug development strategy for identifying new drugs for this disease."

Hugo is the international group of scientists involved in human genetics which is holding a major conference here in April, where Prof Ong will be speaking about his research.

Called the Joint Conference of the Human Genome Meeting 2013 and the 21st International Congress of Genetics, it will be attended by more than 2,000 scientists and researchers and have about 200 speakers.

ailien@sph.com.sg


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