Promising Results for Potential Glioblastoma Multiforme Treatment

New research out of the United Kingdom and Texas suggests a novel approach to treating Glioblastoma Multiforme (GBM), a common and devastating form of brain cancer in adults.

The culmination of a seven-year research project by scientists from the Universities of Surrey, Leeds and Texas and University of Surrey start-up HOX Therapeutics, the study demonstrated in cell and animal models that the HTL-001 peptide is effective at targeting and inhibiting the function of Hox genes, which are believed to be responsible for the growth of GBM.

"People who suffer from Glioblastoma Multiforme have a 5% survival rate over a five-year period—a figure that has not improved in decades,” says Hardev Pandha, project lead and Professor of Medical Oncology at the University of Surrey. “While we are still early in the process, our seven-year project offers a glimmer of hope for finding a solution to Hox gene dysregulation, which is associated with the growth of GBM and other cancers, and which has proven to be elusive as a target for so many years."

Hox genes are responsible for the healthy growth of brain tissue, but are ordinarily silenced at birth after vigorous activity in the growing embryo. However, if they are inappropriately “switched on” again, their activity can lead to the progression of cancer.

One of the many challenges of treating GBM include drug delivery to the tumor site, which is hampered by the presence of the blood–brain barrier (BBB), according to the paper, published recently in BMC Cancer. To make matters worse, GBM effectively also has its own BBB due to abnormal neovasculature with irregular blood flow, further preventing drugs from exiting the circulation, which, in turn, influences the treatment of the tumor when drugs are delivered systemically. Other factors that contribute to a poor prognosis are tumor cell migration into the surrounding tissue, immune evasion, and evasion of cell death induced by radiation and chemotherapy through the activation of anti-apoptotic resistance pathways and upregulation of DNA repair systems.

In vivo biodistribution studies confirmed that HTL-001 was able to cross the BBB. It has also undergone safety testing and is suitable for patient trials. Such trials are now being considered in GBM and other cancers.

"We desperately need new treatment avenues for these aggressive brain tumors, says Professor Susan Short, co-author of the study from the University of Leeds. “Targeting developmental genes like the HOX genes that are abnormally switched on in the tumor cells could be a novel and effective way to stop glioblastomas growing and becoming life-threatening."