The study found that a certain regimen of chemotherapy is more effective on one tumor type, while a different drug works best on the other, setting the groundwork for a more effective approach to treating gastric cancer patients.
"Our study is the first to show that a proposed molecular classification of gastric cancer can identify genomic subtypes that respond differently to therapies, which is crucial in efforts to customize treatments for patients," said Patrick Tan, senior author of the study and associate professor in the Cancer and Stem Cell Biology Program at the Duke-NUS Graduate Medical School.
Earlier a microscopic pathology test developed in 1960 broadly described how well the tumor cells clumped together, typing them intestinal and diffuse - known as the Lauren classification.
"Most gastric cancer patients today are still being treated with a common one-size-fits-all regimen," said Tan, who also serves as group leader at the Genome Institute of Singapore and a senior investigator at the Cancer Sciences Institute of Singapore.
"One reason for this is that the Lauren classification requires significant gastric cancer experience and there is considerable variation in classifying gastric cancers, even among qualified pathologists," Tan said.
But the genetic findings by the Singapore-based researchers add greater specificity to the microscopic classifications and, for the first time, provide some guidance for doctors to prescribe effective treatments.
The team first analyzed 37 gastric cancer cell lines, which were pure cancer cells free of blood, tissue, and other adulterations that could skew results.
Gene expression profiles yielded highly distinct patterns that indicated the two subtypes. In 64 percent of cases, the genetic subtypes validated the Lauren classifications - either intestinal or diffuse. In the other 36 percent of cases, the genomic process distinguished the subtypes where the pathology test could not.
"It was quite reassuring to us that the genomic subtypes were associated with Lauren's system," Tan said. "There is a general assumption in the field that intestinal and diffuse gastric cancers (as classified by Lauren) represent two very different versions of gastric cancer, and now genomic data confirms this by demonstrating that the two genomic subtypes have very different molecular patterns."
The intestinal-type tumors showed significantly better response to the chemotherapies 5-fluorouracil and oxaliplatin, and were more resistant to cisplatin than the diffuse tumors.
"The exact mechanistic reasons for this difference are currently unclear, and this is an area that we are actively working on," Tan said, adding that the researchers are working to find subtype-specific molecular vulnerabilities to drugs.
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