Clinical trial against breast cancer explores the potential anti-tumor role of denosumab

Science and society collaboration is essential for scientific progress, especially in the health and biomedical fields where basic researchers, clinicians and patients are involved, as shown by the initial results of D-BIOMARK. This clinical trial against breast cancer, promoted by the Catalan Institute of Oncology (ICO), has analyzed the potential anti-tumor role of denosumab, a drug already in use in the prevention of metastasis-related osteoporosis and bone lesions. 

The trial is led by Eva González-Suarez, leader of the Transformation and Metastasis research group at IDIBELL and the Spanish National Cancer Research Centre (CNIO); Andrea Vethencourt, clinical researcher in the same group and medical oncologist at ICO; and Catalina Falo, clinical researcher in the IDIBELL Breast Cancer research group and medical oncologist at ICO.

Denosumab acts by inhibiting the RANK pathway, a molecular pathway that has been widely studied in oncology due to its relationship with tumor proliferation and progression, especially in breast cancer.

According to the initial trial results published in Breast Cancer Research, denosumab could boost the anti-tumor immune response by increasing the number of tumor-infiltrating immune cells to fight cancer. This research is based on promising preliminary findings in basic and preclinical research, showing that inhibiting the RANK pathway could help slow down tumor growth.

Basic science: The RANK pathway and its relationship with breast cancer

Normally, a pair of bone metabolism proteins, RANK and RANKL, from which the RANK pathway takes its name, act as information mediators provided by hormones like progesterone and send essential signals for the proper development of the mammary gland. However, if this molecular pathway does not work properly, the mammary cells may start to replicate uncontrollably until cancer arises, according to Eva González-Suárez's findings in previous studies.

RANK pathway inhibitors such as denosumab, seek to interrupt this chain of events. The aim is to prevent the onset of breast cancer or to increase therapeutic efficacy and improve the prognosis of patients when it has already developed.

An advantage of using RANK inhibitors, such as denosumab, is that they are drugs that have already been approved for clinical use and, therefore, have a well-established safety profile, whose side effects are known and manageable in routine practice.

Denosumab boosts the anti-tumor immune response

This clinical trial set out to evaluate the biological effects of denosumab in 60 women with early-stage breast cancer. According to the results, although denosumab was not associated with a reduction in cancer cell proliferation or survival, it was associated with a significant increase in tumor-infiltrating immune cells. The increase was observed in all evaluated breast cancer subtypes, but especially in type B luminal tumors.

Applications in current immunotherapies

Immunotherapy is the strategy that is driving cancer treatment forward, although not equally in all tumor types. In the case of type B luminal tumors, the response rates are relatively low.

The ability of denosumab to increase immune infiltration into the tumor opens up a valuable avenue of clinical interest. Following these results, new analyses have been launched to try to elucidate the mechanisms involved in this immune activation.

Acknowledgement of patients

The researchers and oncologists participating in the study highlight that this result could be achieved thanks to the synergy between basic science, which for years has studied in the lab the ins and outs of the RANK pathway role in breast cancer; the clinical experience of oncologists committed to the search for better treatments; and, especially, the generosity and commitment of the patients who have participated in the trial.

The Spanish National Cancer Research Centre (CNIO) is a public research centre attached to the Ministry for Science, Innovation and Universities.