The retroviral HIV drug HERV-K could be effectively repurposed to treat patients with meningioma and acoustic neuroma, common primary brain tumors.
A recent research breakthrough suggests drugs developed for HIV and AIDS may be able to treat meningioma and acoustic neuroma brain tumors. These tumors are resilient and can return after radiotherapy and surgery, creating a need for alternative therapies.
Meningioma, the most common type of primary brain tumor, is mostly low-grade but can become cancerous over time. It develops from cells located in the meninges, which serve to protect the brain and spinal cord. Acoustic neuroma is a non-cancerous brain tumor that develops in nerve-protecting Schwann cells.
Merlin, a common tumor suppressant, has been shown to aid in the development of meningioma, acoustic neuroma and ependymoma tumors. Many other tumors have been shown to develop mutations to Merlin as well. In this study, investigators used human Merlin-negative schwannoma and meningioma primary cells to investigate how the endogenous retrovirus HERV-K may assist in tumor development.
In typical Schwann cells, ectopic overexpression of HERV-K Env increased and upregulated expression of c-Jun and pERK1/2, known schwannoma, JNK/c-Jun, and RAS/RAF/MEK/ERK tumor pathways. The investigators found that US Food and Drug Administration (FDA)- approved retroviral protease inhibitors ritonavir, atazanavir, and lopinavir reduced the proliferation of schwannoma and grade 1 meningioma cells.
Professor Oliver Hanemann, director of the Brain Tumor Research Center of at the University of Plymouth, said, “The retroviral protease inhibitors ritonavir, atazanavir, and lopinavir—have already been approved for use in the treatment of HIV/AIDS in the USA and are also available in the UK. These results revealed HERV-K proteins to be critical regulators of growth in tumors that are deficient in Merlin.”
High levels of protein produced by the endogenous retrovirus HERV-K DNA have been correlated with the development of various tumors. Indeed, researchers from the Brain Tumor Research Center of at the University of Plymouth found high levels of HERV-K proteins in patients’ meningioma and schwannoma cells. Approved HIV retroviral protease inhibitors targeted the excess proteins to regulate tumor growth.
Brain Tumor Research spokesman Hugh Adams said, “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…This is particularly critical for patients with brain tumors as many of them do not have the luxury of time.”
By identifying HERV-K as a critical regulator of progression in Merlin-deficient tumors, the investigators hope this will guide future strategies for therapeutic intervention.