A blood pressure pill already sitting on pharmacy shelves could give a cancer drug a much bigger reach.
Researchers at Dartmouth Cancer Center said the FDA approved hypertension drug telmisartan significantly boosted the cancer-killing activity of olaparib, a targeted therapy in the PARP inhibitor class. 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 Tyler J. Curiel, MD, MPH, FACP, the study’s senior and lead author.
Olaparib works best in tumors with defects in homologous recombination DNA damage repair, including cancers linked to BRCA gene mutations. Many cancers do not have those DNA repair defects, and tumors that initially respond can become resistant over time.
The Dartmouth team found telmisartan could make tumors more sensitive to PARP inhibitors even if they did not have the DNA repair weaknesses those drugs usually rely on.
In preclinical experiments, combining telmisartan with olaparib increased DNA damage inside cancer cells and activated immune defenses. The combination boosted production of type I interferons, signaling molecules that help the immune system identify and attack cancer.
“This immune activation appears to be a key reason the combination works so well,” Curiel said.
Telmisartan is part of the angiotensin II receptor blocker, or ARB, family of drugs. Researchers compared it with other ARBs and found its cancer-enhancing effects were unique within the class.
The drug also lowered levels of PD-L1 inside tumor cells. Dartmouth said PD-L1 is a protein many cancers use to avoid detection by the immune system.
“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 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.”
Curiel and colleagues at Dartmouth Cancer Center have launched two clinical trials to evaluate the combination. One is testing telmisartan with olaparib in men with metastatic, castration-resistant prostate cancer. According to Curiel, the first participant experienced an exceptional response to treatment.
A second trial recently enrolled its first patient with platinum-resistant ovarian cancer.
“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.”
Dartmouth said support from the Guyre fund and Gmelich fund at Dartmouth Cancer Center helped complete the research and launch the clinical trials.
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