Treatment For Stomach Cancer To Be Decided By Genomic Classification Of Tumors

Researchers in Singapore have found that stomach tumors can be classified into two distinct disease variants that respond differently to chemotherapy.

AsianScientist (Aug. 2, 2011) – Researchers in Singapore have found that stomach tumors can be classified into two distinct disease variants that respond differently to chemotherapy.

The finding, published in Gastroenterology, is the first large-scale genomic analysis of gastric cancer to confirm the two discrete tumor types.

The researchers also 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 Dr. Patrick Tan, senior author of the study and associate professor at Duke-NUS Graduate Medical School.

Gastric cancer is the second leading cause of cancer death worldwide, and is particularly common in East Asia (China, Japan, and Korea). In 2008, there were more than 300,000 diagnosed cases of stomach cancer in China alone, accounting for half of the total number of cases worldwide.

Patients have long had markedly different responses to treatments, suggesting that their tumors may have underlying differences.

A microscopic pathology test developed in the 1960s, known as the Lauren classification, broadly described how well the tumor cells clumped together, typing them as either “intestinal” or “diffuse.”

However, this analysis fell short as a reliable prognostic tool, partly because there is considerable variation in the classification of gastric tumors by different pathologists.

The findings based on genome-wide gene expression analysis by the researchers add greater specificity to the microscopic classifications.

Establishing the highly accurate genomic profiles of tumor subtypes also enabled the researchers to observe differences in their responses to chemotherapy.

The intestinal-type tumors showed significantly better response to the drug combination of 5-fluorouracil and oxaliplatin, and were more resistant to cisplatin than the diffuse-type tumors.

“The exact mechanistic reasons for this difference are currently unclear, and this is an area that we are actively working on,” Dr. Tan said, adding that the researchers are working to find subtype-specific molecular vulnerabilities to drugs.

Based on this work, the researchers have launched a prospective clinical trial in Singapore, called the 3G study, where gastric cancer tumors will be genomically profiled and allocated to specific treatments on the basis of the tumor type. The trial, which began last July, has admitted 17 patients diagnosed with advanced stomach cancer and targets to enroll up to 90 patients.

The article can be found at: Tan IB et al. (2011) Intrinsic Subtypes Of Gastric Cancer, Based On Gene Expression Pattern, Predict Survival And Respond Differently To Chemotherapy.

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Source: Duke University Medical Center.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

Yew Chung is a postdoctoral research fellow at the Duke-NUS Graduate Medical School, Singapore.

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