FDA-approved cancer drug halts Epstein-Barr virus–driven lymphoma growth

Researchers at The Wistar Institute have found that FDA-approved cancer drugs known as PARP1 inhibitors can effectively stop the growth of lymphomas driven by the Epstein-Barr virus (EBV), offering a promising new treatment approach for these aggressive cancers. Published in the Journal of Medical Virology [1], the study reveals that these drugs - already used in other cancers - block EBV’s ability to activate genes that promote tumour growth.

“This isn’t just a new use for an existing drug - it represents a completely different mechanism of action in a viral cancer,” said Dr Italo Tempera, senior author and Associate Professor in the Genome Regulation and Cell Signaling Program at Wistar’s Ellen and Ronald Caplan Cancer Center. “Instead of inducing DNA damage, as seen in other cancers, PARP1 inhibitors in EBV-driven tumours disrupt the virus’s control over the host’s gene expression.

EBV infects more than 90% of the global population. Most remain symptom-free, but immunocompromised individuals - including those with HIV or organ transplants - face higher risks of EBV-associated lymphomas and other cancers. Despite EBV’s clear role in cancer development, no therapies currently target its specific pathways.
Dr Tempera’s team focused on PARP1, an enzyme known for DNA repair, but which also enables EBV to manipulate gene activity in infected cells. “PARP1 acts like a key EBV uses to unlock cancer-promoting genes,” explained Dr Tempera. “Blocking PARP1 denies the virus access.”

Testing talazoparib (BMN 673), a PARP inhibitor approved for breast cancer, in mice with EBV-driven lymphoma yielded striking results: tumour growth dropped by 80%, and cancer spread was significantly reduced - without the usual DNA damage seen with these drugs.

Further analysis uncovered the mechanism: inhibiting PARP1 disrupted the interaction between EBV’s protein EBNA2 and the human oncogene MYC, a key driver of tumour growth. “EBNA2 is like a conductor turning on genes like MYC to orchestrate cancer progression,” said Dr Tempera. “Blocking PARP1 silences the conductor, collapsing the cancer program.”

Because talazoparib is already clinically approved with a well-established safety profile, this discovery could accelerate repurposing for EBV-related cancers. The researchers are now exploring effects in other EBV-driven malignancies such as nasopharyngeal and gastric cancers.

Beyond oncology, the team is investigating PARP1’s role in autoimmune diseases potentially linked to EBV. “Understanding how EBV interacts with host gene regulation opens doors far beyond lymphoma,” Dr Tempera noted. “This is a powerful example of how fundamental virology can lead to new therapies.”

This work was supported by National Institutes of Health grants R01 AI130209 and R01 GM124449 to I.T.; R01 AI153508, R01 CA259171, and R01 DE017336 to P.M.L.; and Core Grant P30 CA010815-53.

More information online

1. PARP1 Inhibition Halts EBV+ Lymphoma Progression by Disrupting the EBNA2/MYC Axis published in the Journal of Medical Virology, 2025. Online publication.