Common blood pressure drug could make cancer therapy far more powerful
A new study from Dartmouth Cancer Center finds that telmisartan, a widely used hypertension medication, significantly boosts the effectiveness of PARP inhibitor cancer drugs, potentially expanding treatment options for more patients.
Researchers at Dartmouth Cancer Center (DCC) have discovered that telmisartan, an FDA-approved drug commonly used to treat high blood pressure, can substantially enhance the cancer-killing activity of the targeted therapy olaparib. The findings, published in The Journal for ImmunoTherapy of Cancer, suggest that this combination could benefit patients whose tumors lack the DNA repair defects typically required for PARP inhibitors to work.
Expanding the reach of PARP inhibitors
Olaparib belongs to a class of targeted cancer drugs called PARP inhibitors, which exploit defects in DNA repair mechanisms in cancer cells. These drugs are particularly effective against tumors with BRCA gene mutations, but many cancers do not have such defects, rendering PARP inhibitors ineffective for a large number of patients. Even when they work initially, tumors often develop resistance. The Dartmouth team showed that telmisartan can make tumors more sensitive to PARP inhibitors, even without the typical DNA repair weaknesses.
Boosting immune response
In preclinical experiments, combining telmisartan with olaparib increased DNA damage inside cancer cells and activated key immune defenses. The treatment boosted production of type I interferons, signaling molecules that help the immune system identify and attack cancer. Additionally, telmisartan lowered levels of PD-L1, a protein many cancers use to evade immune detection. According to senior author Dr. Tyler J. Curiel, this immune activation is a key reason the combination works so well.
Unique among blood pressure drugs
Telmisartan belongs to the angiotensin II receptor blocker (ARB) family. When compared with other ARBs, its cancer-enhancing effects were found to be unique within the class. "Telmisartan has several distinct anticancer effects that could make tumors more responsive to different types of treatments," Curiel said, noting that the team has data showing similar benefits with chemotherapy and immunotherapies.
Clinical trials underway
Because telmisartan is taken orally, has an established safety profile, and is well tolerated even by people without hypertension, researchers believe it is ideal for rapid testing in cancer patients. DCC has launched two clinical trials: one evaluating telmisartan with olaparib in men with metastatic castration-resistant prostate cancer (the first participant showed an exceptional response), and another recently enrolling its first patient with platinum-resistant ovarian cancer. "We are encouraged by what we are seeing so far," Curiel said, adding that the goal is to help more patients benefit from greater effectiveness of PARP inhibitors and potentially overcome resistance.
