Blood pressure drug may boost a key cancer therapy
Dartmouth researchers report that telmisartan improved olaparib’s anticancer effects in preclinical work, with early clinical trials now underway.
By Tom Brennan · Health & Medicine Correspondent
3 min read
A widely used blood pressure medicine may make a major cancer treatment work better for more patients, according to researchers at Dartmouth Cancer Center. The finding could matter for people whose tumors do not have the DNA-repair defects that typically make them vulnerable to PARP inhibitor drugs.
The Dartmouth team reported in the Journal for ImmunoTherapy of Cancer that telmisartan, an FDA-approved hypertension drug, strengthened the effects of olaparib in preclinical studies. Olaparib is a PARP inhibitor, a targeted therapy often used against cancers with weaknesses in homologous recombination DNA repair, including some tumors linked to BRCA mutations.
PARP inhibitors exploit problems in cancer cells’ ability to repair damaged DNA. Dartmouth Health said many tumors lack those specific defects, limiting the number of patients who benefit, and tumors that respond can later develop resistance.
How the combination worked in lab studies
According to Dartmouth Cancer Center, telmisartan made tumors more responsive to olaparib even when they were homologous recombination proficient, meaning they did not have the DNA-repair weakness PARP inhibitors usually target. The research paper by Clare E. Murray, Tyler J. Curiel and colleagues found that telmisartan increased olaparib efficacy by raising type I interferon production.
Dartmouth Health said the drug combination increased DNA damage in cancer cells and activated immune signals that help the immune system recognize and attack tumors. Curiel, the study’s senior and lead author, said the immune activation appears to be a central reason the pairing performed well.
Researchers also found that telmisartan reduced PD-L1 levels inside tumor cells, according to Dartmouth Health. PD-L1 is a protein cancers can use to evade immune detection, so lowering it could add another route by which the treatment combination helps the body attack cancer.
Not all similar blood pressure drugs showed the same effect
Telmisartan belongs to a class of medicines called angiotensin II receptor blockers, or ARBs, commonly prescribed for high blood pressure. Dartmouth researchers compared telmisartan with other ARBs and reported that the cancer-related effects were specific to telmisartan within that group.
Curiel said Dartmouth researchers have also generated data suggesting telmisartan can improve the effects of some chemotherapy classes and immunotherapies in other cancer types through related mechanisms. Those findings were described by Dartmouth Health, but the reported study focused on olaparib and PARP inhibition.
Trials in cancer patients have begun
Because telmisartan is taken orally and has an established safety record, Dartmouth researchers said it is a practical candidate for testing alongside cancer drugs. Curiel and colleagues have started two clinical trials evaluating telmisartan with olaparib.
One trial is studying the combination in men with metastatic, castration-resistant prostate cancer. Dartmouth Health said Curiel reported an exceptional response in the first participant. A second trial has enrolled its first patient with platinum-resistant ovarian cancer.
Dartmouth Health said support from the Guyre fund and Gmelich fund at Dartmouth Cancer Center helped complete the research and start the trials. The clinical studies will test whether the preclinical results translate into broader benefit for patients and whether the approach can help address resistance to PARP inhibitors.
This story draws on original reporting from ScienceDaily.