SINGAPORE: Researchers at the Duke—NUS Graduate Medical School in Singapore have identified numerous new subtypes of gastric cancer that are triggered by environmental factors, paving the way for better understanding and treatment of the killer disease.
They said the insights into the complexities of stomach cancer, which is the second leading cancer killer in the world, show that better ways to diagnose and treat the illness are needed.
Additional work will focus on developing simple diagnostic tests to detect gastric cancer at earlier stages, as well as drugs that are more potent against different subtypes.
The paper’s lead author, Associate Professor Patrick Tan, said the results strongly show that gastric cancer is not one disease but a conglomerate of multiple diseases, each with a different feature.
This explains why patients often responded differently to the same treatment.
Like many cancers, stomach cancer is caused by genetic mutations, as well as external factors that affect the way genes work.
These factors work by methylation, a chemical process in which specific locations along the DNA are modified without actually altering the DNA sequence.
The researchers used 240 primary tumours and cell lines to conduct the first full survey of the DNA methylation landscape in gastric cancer, known as the methylome.
Their goal was to identify new molecular subgroups of gastric cancer not caused by primary genetic mutations, particularly those that might be targeted with therapies.
The researchers found that the gastric cancer methylome was widespread.
They also identified a subgroup of gastric cancers with extremely high levels of methylation.
The Duke—NUS—led team demonstrated in laboratory experiments that these tumours may have increased sensitivity to demethylating drugs.
The research is partly supported by the Singapore National Research Foundation under its TCR Flagship Gastric Cancer Consortium and administered by the Ministry of Health’s National Medical Research Council.
The paper has been published in the Science Translational Medicine.
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