HIV Drugs Could Accelerate Treatment of Low-Grade Primary Brain Tumors

The prognosis for meningioma tumors, the most common type of primary brain tumor, is typically good. Yet there are recurrent and aggressive cases that can be challenging to treat due to lack of treatment alternatives to surgical resection and radiation therapy.

That’s why recent research at University of Plymouth’s Brain Tumour Research Centre could be very good news for patients diagnosed with a primary brain tumor.

Dr. Sylwia Ammoun, senior research fellow, and her collaborator, Dr. Robert Belshaw, investigated the role that specific sections of DNA play in low-grade brain tumor development. In doing so, they believe they have found that drugs already approved to treat HIV may also be able to reduce proliferation of specific tumor cells.

Schwannoma and Meningioma Tumors: What’s Stimulating Growth?

In their study, published recently in Cancer Research, the University of Plymouth team researched the role of endogenous retrovirus HERV-K, sections of DNA that integrated into the genome of human ancestors millions of years ago from ancient germline infections.

HERVs make up about 8% of the human genome. They are classified according to the tRNA primer-binding site—in this case, the lysine (K) tRNA. In the University of Plymouth’s Brain Tumour Research Centre study, high levels of HERV-K proteins were found to be present in meningioma tumor and schwannoma cells obtained from patients. Researchers were also able to identify molecular events that may enable HERV-K proteins to stimulate the growth of these primary brain tumors.

As a result, the University of Plymouth researchers discovered that several FDA-approved retroviral protease inhibitors, such as ritonavir, atazanavir and lopinavir, reduced proliferation of schwannoma and grade I meningioma tumor cells in their laboratory.

“These findings are extremely significant as drug repurposing is a valuable way to accelerate the testing of new approaches into clinical trials which, if successful, could reach patients sooner,” Hugh Adams, spokesman for Brain Tumour Research told ScienceDaily. “This is particularly critical for patients with brain tumours as many of them do not have the luxury of time.”

It takes an average of 13 years and $1.8 billion to develop a new cancer drug in the laboratory and get it approved by the FDA. What’s more, only about 5% of oncology pharmaceuticals are ultimately approved.

Low-Grade Primary Brain Tumors and Precision Medicine

Meningioma tumors account for 39% of patients diagnosed with a primary brain tumor. Because the vast majority of lesions are WHO grade I, meningiomas are largely considered to be “benign” tumors. However, some low-grade meningiomas can have a more aggressive clinical course and behave similarly to high-grade tumors.

Research on brain tumors has historically been underfunded, according to Brain Tumour Research, and any investment is typically focused on high-grade brain tumors such as glioblastomas. Yet the University of Plymouth’s Low-Grade Brain Tumour Centre of Excellence is creating a Brain Tissue Biobank, with 98.7% of the samples from low-grade schwannoma and meningioma tumors.

Researchers are using the biobank to genotype the samples to discover main mutations, ultimately stratifying subtypes of meningioma tumors to enable research into precision medicine.

“Our focus is on the benign end of the spectrum and specifically tumours that arise from the linings of the brain and spinal cord—the meninges,” says Dr. Oliver Hanemann, Director of the Brain Tumour Research Centre of Excellence.

In the hopes of guiding postoperative management decisions for meningiomas, an international group of researchers recently described the distinct clinical outcomes and recurrence rates associated with meningioma molecular subgroups.

In their study of 469 meningiomas, published in Neuro-oncology in May 2021, they identified the HH subgroup as an independent marker for meningioma aggressiveness. They also found that PI3K-activated meningiomas recur earlier than other subtypes.

In terms of this recent breakthrough in precision medicine and primary brain tumors, it turns out that FDA-approved retroviral protease inhibitors may only be able to reduce proliferation of specific tumor cells in low-grade tumors. In contrast, another recent study published in BMC Research Notes on potential improved brain tumor treatment found that HERV-K splice products do not play a role in human malignant gliomas, and therefore cannot be targeted by HIV drugs.