Researchers at Dartmouth Cancer Center have discovered that telmisartan, a widely used blood pressure medication, can dramatically enhance the effectiveness of olaparib, a targeted cancer drug that currently works for only a subset of patients.
The finding, published in The Journal for ImmunoTherapy of Cancer, suggests that combining the two drugs could help many more people benefit from PARP inhibitors, a class of cancer therapies that target specific DNA repair defects in tumors.
Olaparib works by exploiting a weakness in how certain cancer cells repair damaged DNA. The drug is particularly effective against tumors with defects in homologous recombination repair, including cancers linked to BRCA mutations. But most cancers lack these specific vulnerabilities, making PARP inhibitors ineffective for the majority of patients. Tumors that initially respond to the drug often develop resistance over time.
What makes telmisartan's impact significant is its mechanism. In laboratory experiments, the drug made tumors sensitive to olaparib even without the DNA repair defects the therapy typically requires. The combination increased DNA damage in cancer cells while simultaneously triggering immune defenses.
Specifically, the treatment boosted production of type I interferons, signaling molecules that help the immune system identify and attack cancer cells. Telmisartan also lowered levels of PD-L1, a protein many cancers use to hide from immune detection.
"This immune activation appears to be a key reason the combination works so well," said Tyler J. Curiel, MD, MPH, FACP, the study's lead author. "Telmisartan has several distinct anticancer effects that, together with targeted therapy, could make tumors more responsive to distinct types of treatments."
Among blood pressure medications, telmisartan appears to stand alone. Researchers tested other drugs in the angiotensin II receptor blocker family and found that telmisartan's cancer-enhancing effects were unique to this particular medication.
The practical advantages are substantial. Telmisartan is taken by mouth, has an established safety record, and is well tolerated even by people without hypertension. This makes it ideal for rapid testing in cancer patients, according to the researchers.
Clinical trials are already underway. One study is testing the combination in men with metastatic castration-resistant prostate cancer. Curiel reported that the first participant experienced an exceptional response. A second trial recently enrolled its first patient with platinum-resistant ovarian cancer.
The early results have encouraged the research team. "Our goal is to determine whether this combination approach can help more patients benefit from greater effectiveness of PARP inhibitors and other cancer treatment classes and potentially overcome resistance to these drugs," Curiel said.
Author Jessica Williams: "A cheap, safe blood pressure pill that could supercharge cancer drugs isn't just encouraging news,it's the kind of discovery that reshapes treatment options for thousands of patients who currently have nowhere left to go."
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