PPF could limit the spread of glioblastoma multiforme

The Translational Genomics Research Institute (TGen) has identified a drug, propentofylline or PPF, that could help treat patients with deadly brain cancer.

TGen researchers have reported that PPF works to limit the spread of glioblastoma multiforme by targeting a protein called TROY. In addition, TGen laboratory research also found that PPF increases the effectiveness of a standard-of-care chemotherapy drug called temozolomide (TMZ), and radiation, to treat glioblastoma.

“We showed that PPF decreased glioblastoma cell expression of TROY, inhibited glioma cell invasion, and made brain cancer cells more vulnerable to TMZ and radiation,” said Dr Nhan Tran, Associate Professor and head of TGen’s Central Nervous System Tumour Research Lab.

An advantage of small-molecule PPF is that it can penetrate the blood-brain barrier and reach the tumour. And, the FDA has already approved it.

“Our data suggests that PPF, working in combination with TMZ and radiation, could limit glioblastoma invasion and improve the clinical outcome for brain tumour patients,” said Dr Tran.

One of the primary treatments for glioblastoma is surgical removal of the tumour. However, because of the aggressive way glioblastomas invade surrounding brain tissue, it is impossible to remove all parts of the tumours, and the cancer eventually returns and spreads. This insidious cancer invasion also limits the effectiveness of chemotherapy drugs and radiation therapy.

TGen found that PPF works to limit the spread of glioblastomas by targeting and knocking down the expression of the TROY protein. TGen researchers have linked TROY to the cellular mechanisms that enable glioblastomas to invade normal brain cells, and resist anti-cancer drugs.

“New therapeutic strategies that target the molecular drivers of invasion are required for improved clinical outcome,” said Dr Harshil Dhruv, a TGen Research Assistant Professor. “Propentofylline may provide a pharmacologic approach to targeting TROY, inhibiting cell invasion and reducing therapeutic resistance in glioblastomas.”

PPF can cross the blood-brain barrier

One of the fundamental challenges in treating brain cancer with drugs is what is known as the blood-brain barrier that separates circulating blood from the brain extracellular fluid in the central nervous system. This barrier works to protect the brain from toxins. However, this security system is so effective at protecting the brain that it prevents many life-saving drugs — all but some small molecules — from being able to treat cancer and other diseases of the brain.

As a result, there has been little progress in recent decades in finding new effective treatments for glioblastoma multiforme. Median survival for newly diagnosed glioblastoma multiforme patients is only 14.6 months. Only 5 percent of patients survive more than 5 years.

“Clinical trials revealed that PPF can cross the blood-brain barrier, and has minimal side effects,” Dr Tran said. “PPF could be easily translated to the clinic as an adjuvant therapy in combination with standard of care treatment for glioblastoma multiforme patients.”