Researchers Create Molecule That Attacks Cancer Genes' 'Instruction Manual'

Findings from cell, animal experiments may hold promise for rare, fatal cancer, researchers say

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THURSDAY, Sept. 30, 2010 (HealthDay News) -- Researchers have created a molecule that can prevent certain cancer genes from getting instructions from their own internal "manual," raising the possibility that treatments could stop cancer at its source.

In the Sept. 29 issue of Nature, researchers report that the molecule prevents certain cancer cells from dividing so rapidly and causes them to "forget" that they are cancer cells so that they begin to resemble normal cells.

The findings appear in a study that suggests the treatment could help kids and young adults struck by a rare but fatal cancer called NUT midline carcinoma, which is so intractable that no targeted therapy has even been developed for it.

"The disease tends to arise in the chest, head, or neck, along the vertical centerline of the body, with aggressive tumor growth and metastasis," study senior author Dr. James Bradner said in a news release provided from Dana-Farber Cancer Institute. "Patients may have a brief response to chemotherapy, but they eventually succumb to the spread of the disease."

Enter new research into cancer genes. "In recent years, it has become clear that being able to control gene activity in cancer -- manipulating which genes are 'on' or 'off'-- can be a high-impact approach to the disease," Bradner said. "If you can switch off a cancer cell's growth genes, the cell will die. Alternatively, switching on a tissue gene can cause a cancer cell to become a more normal tissue cell."

Researchers first studied the hybrid molecule they created -- called JQ1 -- in cells. JQ1 tricked the NUT midline carcinoma cancer cells by blocking a specific abnormal protein inside them. This substance -- an epigenetic "reader" protein -- issues start and stop commands to cancer genes by reading "bookmark" instructions on a substance called chromatin, which packages the genes' DNA and serves as the slate on which instructions to begin or end activity are written.

The investigators went on to test JQ1 in an animal model. Researchers transplanted the NUT midline carcinoma cells from patients into laboratory mice, which were then given the JQ1 molecule.

"The activity of the molecule was remarkable," says Bradner, who is an associate member of the Chemical Biology Program at the Broad Institute of Harvard and MIT. "All the mice that received JQ1 lived; all that did not, died."

Issuing stop and start commands to such cancer genes may be targets for future cancer treatments, the scientists noted.

"This research further illustrates the promise of the ability to deliver selected molecules to cancer-causing proteins to stop the cancer process while producing a minimum of residual side effects," Bradner said.

The study authors noted that, while the new research appears promising, much additional research and testing is needed before humans might benefit from the therapy.

More information

For more about cancer, visit the U.S. National Library of Medicine.

SOURCE: Dana-Farber Cancer Institute, news release, Sept. 24, 2010


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