A drug long used to treat high blood pressure may help make an important class of cancer drugs even more effective, according to new research from Dartmouth Cancer Center (DCC). The study found that the FDA-approved drug telmisartan significantly increased the cancer-killing activity of the targeted therapy olaparib, raising the possibility that more patients would benefit from the treatment. The survey results are Cancer Immunotherapy Journal.
“This study shows that a common, safe, well-tolerated, convenient and inexpensive drug has the potential to significantly improve the effectiveness of an important type of cancer treatment,” said Tyler J. Kriel, MD, MPH, FACP, senior author and first author of the study.
Bringing PARP inhibitors to more patients
Olaparib belongs to a group of targeted cancer drugs known as PARP inhibitors. These drugs work by exploiting flaws in the way certain cancer cells repair damaged DNA. They are particularly effective against tumors that have problems with homologous recombination DNA damage repair, such as cancers associated with BRCA gene mutations.
However, many cancers lack these DNA repair defects. This means that PARP inhibitors are ineffective for many patients. Even if drugs are initially effective, tumors often become resistant to them over time.
The Dartmouth research team found that telmisartan can increase the sensitivity of tumors to PARP inhibitors even when they do not have the DNA repair weaknesses that PARP inhibitors normally rely on.
Enhanced immune response to tumors
In preclinical experiments, combining telmisartan and olaparib increased DNA damage within cancer cells while also activating important immune defenses. This combination of treatments stimulated the production of type I interferon, a signaling molecule that helps the immune system identify and attack cancer.
“This immune activation seems to be the main reason why this combination works so well,” Kriel said.
Unique effects among blood pressure drugs
Telmisartan is part of the angiotensin II receptor blocker (ARB) family of drugs that are widely prescribed to treat hypertension. Researchers compared telmisartan to other ARBs and found that its cancer-enhancing effects were unique within its class.
The drug also reduced PD-L1 levels within tumor cells. PD-L1 is a protein that many cancers use to avoid detection by the immune system, making this additional effect a potential advantage.
“Telmisartan has several different anti-cancer effects, and when used in combination with targeted therapies, it may make different types of tumors more responsive to treatment,” Curiel said. “While we showed improved efficacy with PARP inhibitors in this study, we also have excellent data showing that telmisartan improves the efficacy of different types of chemotherapy and immunotherapy in many other cancer types through related mechanisms.”
Early clinical trials already underway
Because telmisartan is taken orally, has established safety, and is well tolerated even in people without high blood pressure, researchers believe that telmisartan is suitable as a rapid test for cancer patients. DCC’s Curiel and colleagues have already begun two clinical trials to evaluate this combination.
One study is testing telmisartan and olaparib in men with metastatic castration-resistant prostate cancer. According to Kriel, the first participants experienced an extraordinary response to the treatment. The second trial recently enrolled its first patient with platinum-resistant ovarian cancer.
“We’re encouraged by what we’ve seen so far,” Kriel said. “Our goal is to determine whether this combination approach allows more patients to benefit from the greater efficacy of PARP inhibitors and other types of cancer treatments and potentially overcome resistance to these drugs.”
Support from DCC’s Guyre Fund and Gmelich Fund played a key role in completing the study and starting clinical trials.
