By Steven O. Mukoro
A widely prescribed blood pressure medication may hold the key to making a major class of cancer drugs far more effective, potentially extending their benefits to many patients who currently do not respond to treatment.
Researchers at Dartmouth Cancer Centre have discovered that telmisartan, an FDA-approved drug commonly used to treat hypertension, can significantly enhance the cancer-fighting effects of olaparib, a targeted therapy known as a PARP inhibitor. The findings, published in The Journal for ImmunoTherapy of Cancer, have already led to early-stage clinical trials in cancer patients following promising results in preclinical studies.
According to the research team, the combination not only increases the ability of olaparib to destroy cancer cells but also stimulates the body’s immune system to mount a stronger attack against tumours.
“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 Dr. Tyler J. Curiel, the study’s senior and lead author.
Expanding the Reach of PARP Inhibitors
Olaparib belongs to a class of targeted cancer treatments known as PARP inhibitors, which are designed to exploit weaknesses in the DNA repair systems of cancer cells. These drugs have proven particularly effective in tumours carrying defects in homologous recombination DNA repair pathways, including cancers associated with BRCA gene mutations.
However, many tumours lack these genetic vulnerabilities, limiting the number of patients who can benefit from PARP inhibitors. In addition, cancers that initially respond often develop resistance, reducing the long-term effectiveness of treatment.
The Dartmouth researchers found that telmisartan can make tumours more susceptible to PARP inhibition, even when they do not possess the DNA repair defects typically required for these drugs to work.
Boosting the Immune System’s Cancer-Fighting Ability
Laboratory studies revealed that the combination of telmisartan and olaparib increased DNA damage within tumour cells while simultaneously activating powerful immune responses.
One of the most significant findings was the enhanced production of type I interferons – important signalling molecules that help the immune system recognise and attack cancer cells more effectively.
“This immune activation appears to be a key reason the combination works so well,” Curiel explained. The researchers also discovered that telmisartan reduced levels of PD-L1, a protein many tumours use to evade immune surveillance. By lowering PD-L1 expression, the drug may help expose cancer cells to attack by the immune system.
A Unique Advantage Among Blood Pressure Drugs
Telmisartan belongs to the angiotensin II receptor blocker (ARB) family, a group of medications widely prescribed for hypertension. When scientists compared telmisartan with other ARBs, they found that its ability to enhance cancer treatment appeared to be unique within the drug class.
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According to the investigators, telmisartan exerts multiple anti-cancer effects that could complement a range of treatment strategies.
“Telmisartan has several distinct anticancer effects that, together with targeted therapy, could make tumours more responsive to distinct types of treatments,” Curiel said. “We showed the improved efficacy with PARP 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 Trials Already in Progress
Because telmisartan is inexpensive, orally administered and has a long-established safety profile, researchers believe it can be rapidly incorporated into clinical testing.
To evaluate its potential in patients, Dartmouth Cancer Centre has already launched two clinical trials. One is investigating the combination of telmisartan and olaparib in men with metastatic castration-resistant prostate cancer, while another is testing the approach in patients with platinum-resistant ovarian cancer.
Researchers reported that the first participant enrolled in the prostate cancer study experienced an exceptional response, while the ovarian cancer trial has recently begun recruiting patients.
Although the studies are still in their early stages, investigators are optimistic that the strategy could help overcome one of the major limitations of PARP inhibitors and potentially improve outcomes across multiple cancer types.
“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 inhibitors and other cancer treatment classes and potentially overcome resistance to these drugs.”
If confirmed in larger human studies, the findings could offer a simple and cost-effective way to boost the power of existing cancer therapies using a medication that has already been safely used by millions of people worldwide.
In finishing with the study and launching the clinical tests, an important role was played by Guyre fund and Gmelich fund at DCC via financial assistance.
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