Colon Cancer Genomic Mapping May Point Toward Therapies

The largest study of colon cancer tumors to date found new mutations that may cause malignancy in various organs, bolstering research that links the disease more to specific genetic changes than its location in the body.

Researchers sequenced the genomes of 276 tumors, then compared the results with normal cells from the same patients. They found some mutations previously linked to other types of cancer, and new variants that may be targeted by therapies currently in development, said Raju Kucherlapati, a professor at Harvard Medical School and an author of the study.

“It turns out there were a number of novel and very interesting things that tell us about the biology of the tumors, and also point to directions in which therapies can go,” Kucherlapati said in a telephone interview. “Some of the same genes are modified or mutated in many different cancers.”

The research published yesterday by the journal Nature is among recent studies showing how medicines designed to target gene mutations in one cancer may be applied to other malignancies with the same abnormality. These results have spurred drugmakers such as Bristol-Myers Squibb Co. (BMY), Pfizer Inc. (PFE) and Roche Holding AG (ROG), the world’s biggest maker of cancer medicines, to focus their cancer research on so-called targeted therapies.

About 5 percent of patients in the study had tumors with mutations to the ERBB2 gene, which also has been found in breast and gastric cancers. Herceptin, a $6 billion breast cancer drug from Basel, Switzerland-based Roche, targets that mutation, Kucherlapati said. Herceptin was one of the first cancer medicines aimed at patients whose tumors have this genetic abnormality.

Gene Target

Another potential target for drugmakers is a mutation that caused 22 percent of patients in the study to have high levels or over-expression of the insulin-like growth factor-2 gene. Companies currently working on inhibitors for this gene, include London-based AstraZeneca’s Medimmune unit, which is testing its therapy, MEDI 573, in the first of three trials typically required for regulatory approval.

Other drugmakers are expanding testing of their cancer therapies that focus on specific gene variants. In May, New York-based Pfizer found that Xalkori, its drug that targets adult lung cancer caused by a gene defect, also eradicates the malignancy in some children with rare tumors of the nerves, blood and soft tissue. Bristol-Myers, based in New York, also announced in May it would expand testing of its leukemia drug Sprycel in patients with lung cancer because it appeared to help one patient with a particular mutation.

The data released yesterday are part of a broader project by the National Institutes of Health called the Cancer Genome Atlas, which is analyzing tumors and blood samples from 20 types of cancer.

One of the project’s earlier studies of ovarian cancer patients with a genetic mutation best known for its ties to breast cancer have found they have a higher survival rate than those without the mutation.

To contact the reporter on this story: Ryan Flinn in San Francisco at rflinn@bloomberg.net

To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net

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