'East Asian gene' explains resistance to cancer drugs

SINGAPORE - Scientists in Singapore have discovered the reason why certain highly successful cancer drugs do not work on some people of East Asian descent. 

The reason: A common variant of a gene displayed in about 15 per cent of East Asians.

No people of European or African ancestry were found to have this gene variant.

According to the researchers, tyrosine kinase inhibitor drugs (TKIs) work effectively in most patients to fight certain blood cell cancers by shutting down molecular pathways that keep these cancers flourising.

The gene provides resistance against TKI drugs, due to the impaired production of the gene protein.

The multinational team, led by researchers from Duke-NUS Graduate Medical School, estimated that some 14,000 newly diagnosed leukaemia and lung cancer patients each year will carry the gene variant.

Discovering how the gene variant caused the resistance also allowed the researchers to overcome it.

A novel class of drugs called the BH3-mimetics provided the answer, said S. Tiong Ong, senior author of the study and associate professor at Duke-NUS.

When the new class of drugs was added to current therapies, they were able to overcome the resistance conferred by the gene as they restored the function of the gene variant which allows it to respond to the drug. 

“While it’s interesting to learn about this ethnic difference for the mutation, the greater significance of the finding is that the same principle may apply for other populations,” said Patrick Casey, Ph.D., senior vice dean for research at Duke-NUS.

“There may well be other, yet to be discovered gene variations that account for drug resistance in different world populations," he said.

He further highlighted the importance for researchers to understand he differences in cancer pathways, mutations, and treatments that work for different types of individuals.

This will pave the way for personalised cancer treatment and, ultimately, control cancer, he predicted.

The next step would be to begin clinical trials. The researchers announced that they are working with the commercialisation arm of the Agency for Science, Technology & Research (A*STAR), to develop a clinical test for the gene variant.

This is so that the discovery can be quickly brought to patients.

The major contributors to the study include additional researchers and teams from the Duke-NUS Graduate Medical School, Genome Institute of Singapore (Dr. Yijun Ruan and Dr. Axel Hillmer), Singapore General Hospital (Dr. Charles Chuah), and National Cancer Centre Singapore (Dr. Darren Wan-Teck Lim).

yamadak@sph.com.sg