Mechanism in cells forming brain tumours may offer target for gene therapy

Washington, Oct 25 : In a new study, researchers at Cedars-Sinai Medical Center's Maxine Dunitz Neurosurgical Institute have discovered a molecular mechanism involved in the development of cells that give rise to malignant brain tumours.

The scientists say that their findings may provide a target for killing malignant brain tumours at their source, and will also prevent them from recurring. Cancer stem cells, like normal stem cells, have multi-potent and self-renewing properties, but instead of producing healthy cells, they propagate cancer cells. Thus, destroying such "mother cells" would mean that the tumour would not survive.

Alternatively, if such cells are not removed or destroyed, the tumour would continue to return despite the use of existing cancer-killing therapies.

Glioblastoma multiforme is the most malignant form of tumour that develops in the brain, but all glioblastomas are not identical. Subgroups are comprised of cells originating from different brain tumour stem cells with unique genetic characteristics that use different signalling pathways in their development and growth.

Now, the researchers are building genetic "profiles" of these cancer stem cells and the tumours they appear to produce.

In the current study, they identified a subset of brain tumour stem cells that is dependent on a protein called Sonic Hedgehog, and another subset that is not Hedgehog dependent.

Brain tumours resulting from each subset did have the "signalling dependency" characteristics of the mother cells. Pathway-specific blocking interventions prevented the brain tumour stem cells from being able to renew themselves in laboratory experiments and studies in laboratory mice.

According to scientists, Sonic Hedgehog signalling mechanism looks like one of the molecular mechanisms regulating both normal stem cell growth and cancer stem cell growth.

"According to our analysis, patients who have malignant brain tumors produced from cancer stem cells that rely on this mechanism have a shorter survival than those who don't," said John S. Yu, M.D., director of Surgical Neuro-oncology at Cedars-Sinai and senior author of the Stem Cells article.

The findings could pave the way for therapies to block the underlying cancer-causing mechanisms with genes or small molecules, according to the research team.

The study is published in the journal Stem Cells.

ANI