Blood Pressure Drug Telmisartan Shows Promise in Enhancing Cancer Treatment Effectiveness
核心洞察
Dartmouth Cancer Center researchers found that telmisartan, an FDA-approved blood pressure medication, significantly enhances the cancer-killing activity of olaparib, a targeted cancer therapy.
The drug combination increased DNA damage in tumor cells and boosted type I interferon production, helping the immune system recognize and attack cancer more effectively.
Two clinical trials are currently underway testing the combination in metastatic prostate cancer and platinum-resistant ovarian cancer patients.
Dartmouth Cancer Center researchers have discovered that telmisartan, a commonly prescribed blood pressure medication, can significantly enhance the effectiveness of olaparib, a targeted cancer therapy, potentially expanding treatment options for many more cancer patients.
The preclinical study, led by clinical researcher Tyler J. Curiel, MD, MPH, FACP, found that the FDA-approved hypertension drug makes tumors more vulnerable to PARP (搜索) inhibitors even when they lack the specific DNA repair defects that usually make these treatments effective. The findings were published in The Journal for ImmunoTherapy of Cancer.
"This study shows that a common, safe, tolerable, convenient, and inexpensive drug may significantly improve how well an important class of cancer therapies works," said Curiel, the study's senior and lead author.
Overcoming Treatment Limitations
PARP (搜索) inhibitors such as olaparib work by exploiting weaknesses in how some cancer cells repair damaged DNA. They are particularly effective in tumors with defective homologous recombination DNA damage repair, such as those with gene mutations in BRCA (搜索). However, many tumors lack these defects, limiting the number of patients who can benefit from PARP inhibitors. Additionally, most cancers eventually develop resistance to PARP inhibitors.
In laboratory and animal models, the research team discovered that telmisartan causes more damage to cancer cells' DNA when combined with olaparib, thus helping the immune system recognize and attack certain types of tumors. The combination increased the production of type I interferons, which are molecules that help the immune system recognize and attack cancer.
"This immune activation appears to be a key reason the combination works so well," Curiel said.
Unique Properties Among Blood Pressure Medications
Telmisartan belongs to the angiotensin II receptor blocker (ARB) class of medications, commonly prescribed to treat hypertension and reduce heart attack and stroke risk. However, the study found that the cancer-enhancing effects were unique to telmisartan among all the ARBs tested.
The drug also reduced levels of PD-L1 (搜索) inside tumor cells—a protein that cancers use to evade immune attack—further increasing its therapeutic potential. Other types of angiotensin II receptor blockers did not demonstrate the same anti-cancer properties.
"Telmisartan has several distinct anticancer effects that, together with targeted therapy, could make tumors more responsive to distinct types of treatments," Curiel said. "We showed the improved efficacy with PARP (搜索) inhibitors in this study, but we also have good data showing that telmisartan improves efficacy of distinct chemotherapy classes and immunotherapies in many other cancer types through related mechanisms."
Clinical Translation Underway
The researchers at Dartmouth are currently testing telmisartan's effect on patients in two clinical trials. One trial is evaluating the combination in men with metastatic, castration-resistant prostate cancer. The first patient enrolled in the study experienced what Curiel described as an exceptional response to treatment.
A second study, focused on platinum-resistant ovarian cancer, has just begun enrolling patients. The researchers noted that telmisartan is orally bioavailable, safe, and well-tolerated, including by individuals without hypertension, making it an ideal candidate for clinical translation.
Study Limitations and Expert Perspective
The main limitation of the study is that it relied on laboratory models and did not include any human patients. Joshua G. Cohen, MD, medical director of the Gynecologic Cancer Program at City of Hope Orange County in Irvine, California, who was not involved in the study, noted that "at this stage, the idea is still very early in development, and the evidence comes primarily from laboratory studies, not studies in people."
While telmisartan was shown to be effective against tumors with damaged DNA, the researchers found that it may not work as well for cancers that don't have these defects. Most cancers may also develop resistance to olaparib over time, leading it to become less effective. No long-term outcomes or survival data are available yet.
"Much more research—including clinical trials—is needed to determine whether combining telmisartan with PARP (搜索) inhibitors is safe or effective for treating ovarian cancer," Cohen said. "Patients considering these medications together should speak with their cancer care team, who can help them understand what is known, what remains uncertain and what is safest for their individual situation."
"We are encouraged by what we are seeing so far," Curiel said. "Our goal is to determine whether this combination approach can help more patients benefit from greater effectiveness of PARP (搜索) inhibitors and other cancer treatment classes and potentially overcome resistance to these drugs."