Dartmouth Cancer Center (DCC) researchers have discovered that an existing, widely used blood pressure medication may help improve the effectiveness of certain cancer treatments—potentially expanding their use to many more patients and reducing toxicities.

In a new study led by clinician-scientist Tyler J. Curiel, MD, MPH, FACP, investigators found that the FDA-approved blood pressure drug telmisartan can significantly enhance the cancer-killing activity of the targeted cancer therapy olaparib.

“This study shows that a common, safe, convenient, tolerable, and inexpensive once-daily pill may significantly improve how well an important class of cancer therapies works,” said Curiel.

Exploiting cancer’s weakness
PARP inhibitor drugs, such as olaparib, work by exploiting weaknesses in how some cancer cells repair damaged DNA. PARP inhibitors are particularly effective in tumors with certain gene mutations. However, many tumors lack these mutations, limiting the number of patients who can benefit from these drugs. Cancers can also eventually develop resistance to PARP inhibitors.

In early studies, Curiel’s team discovered that when combined with olaparib, telmisartan can make tumors more vulnerable to PARP inhibitors, even when the tumors lack the gene mutations that usually make this type of drug effective.

The combination also stimulated an immune response within the tumor. Specifically, the combination of the two drugs fueled the production of a type of molecule that helps the immune system recognize and attack cancer.

“This immune activation appears to be a key reason the combination works so well,” Curiel said.

Unique among blood pressure drugs

Telmisartan belongs to a class of medications called “angiotensin II receptor blockers” (ARBs), commonly prescribed to treat hypertension, or high blood pressure. But the DCC study found that the cancer-treatment-enhancing effects were unique to telmisartan among all of the ARBs tested.

Telmisartan also reduced levels of a protein inside tumor cells that cancers use to evade immune attack—further increasing its therapeutic potential.

“This study was about PARP inhibitors,” Curiel said. “But we also have a lot of evidence that telmisartan makes certain other chemotherapies and immunotherapies more effective through related mechanisms. Its potential could therefore extend to many other types of cancers and treatments.”

Bench to bedside: clinical trials
Telmisartan’s widespread use and high tolerability, even in people without high blood pressure, make it ideal for clinical use. Curiel’s team is already using the combination strategy in patients through two ongoing clinical trials at DCC.

One trial is for men with metastatic, castration-resistant prostate cancer. The first patient enrolled in the study experienced what Curiel described as an exceptional response to treatment. The second trial is in platinum-resistant ovarian cancer, which just enrolled its first patient.

“We are encouraged by what we are seeing so far,” Curiel said. “We have multiple trials in development to determine whether this approach can help more patients benefit from more effective cancer treatments.”