Research shows that a widely used antihypertensive drug in clinical practice may help a large class of cancer-targeted drugs to achieve efficacy far beyond expectations, bringing new hope to some patients who originally had limited benefit. Researchers at Dartmouth Cancer Center (DCC) in the United States have discovered that telmisartan, a commonly used oral drug used to treat high blood pressure, can significantly enhance the tumor-killing ability of the targeted anti-cancer drug olaparib. Relevant results were recently published in the Journal for ImmunoTherapy of Cancer.
Lynparza is a PARP inhibitor, a class of drugs that "take advantage of" DNA damage repair defects in cancer cells to achieve precise strikes. It is particularly suitable for tumors with homologous recombination DNA repair dysfunction, such as cancers with BRCA gene mutations. However, many tumors do not have such repair defects, limiting the applicable population of PARP inhibitors, and some cancers will gradually become resistant to these drugs during treatment.
The research team found that even in tumors without typical DNA repair defects, telmisartan can significantly increase tumor sensitivity to PARP inhibitors. In preclinical experiments, tumors treated with telmisartan plus olaparib showed more signs of DNA damage and activated stronger immune-related signals than those treated with olaparib alone. In particular, this combination therapy significantly increased the production of type I interferon, which helps the body's immune system recognize and attack cancer cells more effectively.
Study leader Tyler J Curiel said this immune activation appears to be one of the key reasons for the significantly improved efficacy of the combination therapy. He noted that the discovery of a drug that is "common, safe, well-tolerated, easy to use and cheap" could significantly improve the effectiveness of an important class of cancer treatments, a finding that has important clinical potential.
Telmisartan belongs to the angiotensin II receptor blocker (ARB) class of antihypertensive drugs commonly used clinically. In this DCC study, in the comparative test of multiple ARB drugs, only telmisartan showed a clear and unique effect of "enhancing the effect of cancer treatment". In addition, telmisartan can also reduce the level of PD-L1 in tumor cells - PD-L1 is a protein that helps tumors evade immune attack. Its reduced expression is expected to further enhance the body's immune system's ability to clear cancer cells.
Currier noted that telmisartan exhibits multiple potential anti-cancer effects and, when combined with targeted therapies, can make tumors more sensitive to many different types of treatments. This study confirmed its improved efficacy when combined with PARP inhibitors, but the team also has strong data showing that in various other cancer types, telmisartan can also improve the efficacy of some chemotherapy drugs and immunotherapy drugs through similar mechanisms.
Since telmisartan is an oral drug and has been widely used in the field of hypertension treatment for a long time, and is generally safe and well-tolerated in a large number of people, including people without hypertension, it is considered very suitable to be the first to enter clinical trials as a "repurposing old drug" solution. Currently, the DCC team has launched two clinical trials to conduct preliminary verification of this combined treatment strategy.
One trial is recruiting patients with metastatic castration-resistant prostate cancer to evaluate the combination of telmisartan and olaparib, with the first subject reportedly having a "very significant response." Another trial focuses on platinum-resistant ovarian cancer and has enrolled its first patient. The research team said that the current early clinical results are encouraging, and they hope to further confirm whether this combination therapy can help more patients obtain more lasting and obvious benefits from PARP inhibitors and other cancer treatment options, and overcome the resistance problem of existing therapies to a certain extent.