miércoles, 25 de enero de 2012

Epigenetic Study Suggests Possible Treatment for Retinoblastoma ► NCI Cancer Bulletin for January 24, 2012 - National Cancer Institute

NCI Cancer Bulletin for January 24, 2012 - National Cancer Institute


Epigenetic Study Suggests Possible Treatment for Retinoblastoma

Based on a new model of the genetic and epigenetic changes underlying the childhood cancer retinoblastoma, researchers have identified a potential strategy for treating this rare disease. The model, published online in Nature January 11, suggests that inhibiting a protein called spleen tyrosine kinase (SYK) could benefit patients with this cancer of the eye.

Drugs that inhibit SYK are being developed to treat blood cancers and certain other diseases. In cell cultures and animal models, two of these drugs killed retinoblastoma cells, researchers with the Pediatric Cancer Genome Project found.

Both copies of a gene called RB1 are inactivated in nearly all retinoblastomas, but other molecular changes are required for the disease to progress rapidly. To identify additional DNA alterations, the researchers sequenced the tumor and normal genomes of four affected patients.

The analysis did not reveal any suspicious mutations or structural changes in the genome, however. “This was really surprising,” said Dr. Michael Dyer of St. Jude Children’s Research Hospital and the study’s senior author. “We wondered how these tumors could progress as rapidly as they do.”

In a further analysis based in part on a previous study, the authors focused on epigenetic changes, including DNA methylation and histone modification, which can alter the activity of genes without causing changes in the DNA sequence. When they compared the epigenetic profiles of normal cells and cancer cells, new clues about the disease emerged.

Several cancer-related genes in retinoblastoma cells appeared to be regulated by epigenetic mechanisms, including the SYK gene.

Although SYK has no known function in the eye, the protein may increase the production of a protein called MCL1 that is important for the survival of retinoblastoma cells. Blocking SYK may reduce the amount of MCL1 and trigger the death of retinoblastoma cells, the study authors said.

As a next step, the researchers have begun to develop a formulation of the most relevant SYK inhibitor, called R406, for the eye. The new formulation might provide a way to get more of the drug into the eye, Dr. Dyer said. But the researchers need to assess the potential toxicities of this version of the drug before planning a clinical trial, he added.

No hay comentarios:

Publicar un comentario