The breast cancer clinical trial is investigating the potential antitumor role of denosumab

The breast cancer clinical trial is investigating the potential antitumor role of denosumab

Collaboration between science and society is essential for scientific progress, particularly in health and biomedical fields involving basic researchers, clinicians and patients, as shown by the initial results from D-Biomark. This breast cancer clinical trial, funded by the Catalan Institute of Oncology (ICO), analyzed the potential antitumor role of denosumab, a drug already used in the prevention of metastasis-related osteoporosis and bone lesions.

The study is led by Eva González-Suarez, head of the Transformation and Metastasis research group at Idibell and the Spanish National Cancer Research Center (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 works by inhibiting the rank pathway, a molecular pathway widely used in oncology due to its relationship to tumor proliferation and progression, particularly in breast cancer.

According to the first experimental results published inBreast cancer researchDenosumab could boost the antitumor 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 tumor growth.

Basic science: The rank path and its relationship to breast cancer

Normally, a pair of bone metabolic proteins, Rank and Rankl, from which the Rank pathway gets its name, act as information mediators of hormones such as progesterone and sending essential signals for the proper development of the mammary gland. However, when this molecular pathway does not function properly, the breast cells can start to function uncontrollably until cancer develops, according to Eva González-Suárez's findings in previous studies.

Rank pathway inhibitors such as denosumab attempt to interrupt this chain of events. The aim is to prevent the onset of breast cancer or to increase therapeutic effectiveness and improve the prognosis of patients if 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, the side effects of which are known and manageable in routine practice.

Denosumab increases the antitumor immune response

This clinical trial evaluated the biological effects of denosumab in 60 women with early 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 breast cancer subtypes examined, particularly in type B luminal tumors.

Applications in current immunotherapies

Immunotherapy is the strategy that advances cancer treatment, although not equally across all tumor types. For luminal type B tumors, response rates are relatively low.

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

Recognition of patients

The researchers and oncologists involved in the study show that this result can be achieved thanks to the synergy between basic science that has spent years studying in the laboratory the ins and outs of the role of the rank-pathway role in breast cancer. the clinical experience of oncologists committed to finding better treatments; and especially the generosity and commitment of the patients who took part in the study.

The Spanish National Cancer Research Center (CNIO) is a public research center linked to the Ministry of Science, Innovation and Universities.

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