Potential gene target for deadly childhood cancer identified

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London, Oct 16 : A team of scientists has discovered a new way to potentially block the growth of neuroblastoma - a type of cancer behind 15 percent of all cancer deaths in kids.

Working with human cell lines and tissue samples, researchers explain how they were able to short-circuit genetic processes that apparently contribute to neuroblastomas - tumours that arise from the developing nervous system in children and often appear in the abdomen, chest or neck.

Concentrating on a gene known as ALK, the scientists used a small-molecule inhibitor, a technique common to many drugs, to block abnormalities that apparently cause neuroblastomas.

The team, led by Dana-Farber Cancer Institute researchers Rani E. George, M.D., Ph.D., an assistant professor of paediatrics at Harvard Medical School, and A. Thomas Look, M.D., a professor of paediatrics at Harvard, analysed the ALK gene in 94 tumours representative of general neuroblastomas and 30 neuroblastoma cell lines.

They found that ALK abnormalities in a subset of neuroblastoma cells appear to interfere with the natural cell-death processes.

They also found that some of the ALK mutations were sensitive to a tiny organic molecule known as TAE684, a discovery that may be useful in efforts to create drugs to staunch cancer growth.

Besides this, the researchers used gene-transfer techniques to initiate ALK-related cancer in rodent cells. These transduced neuroblastomas also appear vulnerable to the small molecule, known as an ALK inhibitor.

The current findings dovetail with the recent discovery of the role of ALK mutations in both inherited and non-inherited versions of neuroblastoma.

"This research group looked at neuroblastoma in a totally different and complementary way to ours and came up with similar results, validating the role of ALK mutations. A unique aspect of their work is they proved in a model system that these mutations can indeed be cancer-causing, " Nature quoted paediatric oncologist Yael P. Mosse, M.D., of The Children's Hospital of Philadelphia, as saying.

With samples and data they had collected, scientists traced the genetic roots of many neuroblastomas to ALK mutations - findings that open the door to genetic screenings for the disease as well as possible therapies.

Ultimately, researchers hope drug treatments can be developed to disrupt the cancer cell-signaling process.

The study is published in the online issue of Nature.

ANI

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