Rediscovering denosumab: Exploring its potential as a treatment for breast cancer

Denosumab, widely recognized for its role in preventing osteoporosis and managing bone metastases, is now emerging as a promising candidate in breast cancer therapy. Recent clinical research highlights how this medication, originally designed to inhibit bone resorption by targeting the RANK pathway, may also boost the body's immune response against breast tumors.

The clinical trial led by experts from the Spanish National Cancer Research Centre (CNIO) and IDIBELL involved 60 women with early-stage breast cancer. The study investigated denosumab's biological effects beyond its bone-protective functions. Although the drug did not significantly reduce tumor cell proliferation, a notable increase in tumor-infiltrating immune cells was observed across all breast cancer subtypes, especially in luminal B tumors. This immune activation suggests that denosumab could enhance the effectiveness of immunotherapy approaches.

Central to denosumab's potential in cancer treatment is its ability to inhibit the RANK pathway—a molecular signaling route that, when dysregulated, contributes to tumor growth and progression. In normal physiology, RANK and RANKL proteins regulate bone metabolism and mammary gland development. However, abnormal activation can lead to uncontrolled cell proliferation and cancer development. By blocking this pathway, denosumab may not only prevent tumor growth but also modify the tumor microenvironment to favor immune attack.

Known for its safety profile due to prior approval for osteoporosis and bone-related complications, denosumab offers the advantage of being a readily available therapeutic tool. This positioning allows for quicker integration into cancer treatment protocols, especially as part of combined strategies involving immunotherapy.

The promising findings suggest that denosumab helps reinvigorate the immune system within the tumor microenvironment, increasing immune cell infiltration. This could be crucial for tumors like luminal B breast cancers, which traditionally respond poorly to immunotherapy alone. Ongoing research aims to uncover the mechanisms behind this immune activation, which could lead to novel treatment combinations and improved patient outcomes.

Overall, this emerging evidence underscores the importance of collaborative efforts between basic science, clinical research, and patient participation to advance cancer therapies. As further studies confirm these initial findings, denosumab might soon find a new role—not just in bone health but also as a component of innovative immuno-oncology treatments.

Source: https://medicalxpress.com/news/2025-05-rediscovering-denosumab-osteoporosis-medication-treatment.html