Telmisartan Boosts Cancer Therapy Efficacy, Potentially Expanding Olaparib's Reach
A new study conducted at the Dartmouth Cancer Center (DCC) indicates that the FDA-approved blood pressure medication telmisartan can significantly enhance the cancer-killing activity of olaparib, a targeted therapy. This finding suggests a potential expansion of olaparib's use to a wider range of patients.
This groundbreaking research proposes that telmisartan can significantly enhance the effectiveness of olaparib, potentially broadening its application to more cancer patients.
Enhancing PARP Inhibitor Efficacy
PARP inhibitors, including olaparib, function by exploiting weaknesses in cancer cells' DNA repair mechanisms. These therapies are typically effective in tumors with defective homologous recombination DNA damage repair, such as those with BRCA gene mutations.
However, a significant number of tumors do not possess these specific defects, thereby restricting the patient population that can benefit from PARP inhibitors. Furthermore, many cancers eventually develop resistance to these vital inhibitors.
The research team discovered that telmisartan can increase the susceptibility of tumors to PARP inhibitors, even when the tumors lack the specific DNA repair defects typically associated with PARP inhibitor effectiveness. This represents a significant step towards overcoming existing limitations.
Unique Therapeutic Mechanisms
In preclinical studies, the combination of telmisartan and olaparib yielded multiple benefits. It not only increased DNA damage within tumor cells but also activated powerful immune-stimulating signals.
Specifically, this combination boosted the production of type I interferons, molecules that play a crucial role in aiding the immune system to recognize and combat cancer cells effectively.
The study also found that these cancer-enhancing effects were specific to telmisartan among all the angiotensin II receptor blockers (ARBs) tested. Additionally, telmisartan reduced levels of PD-L1 inside tumor cells, a protein that cancers utilize to evade immune attacks, further contributing to its therapeutic potential.
Clinical Trials Underway
Given telmisartan's oral bioavailability, established safety, and tolerability—even in individuals without hypertension—it is considered a highly suitable candidate for clinical translation.
Researchers at DCC are currently testing this promising strategy in patients through two ongoing clinical trials.
One trial is evaluating the combination in men with metastatic, castration-resistant prostate cancer. The first patient enrolled in this trial demonstrated what was described as an exceptional response, offering early encouragement. The second trial is for platinum-resistant ovarian cancer and has recently enrolled its first patient.