Radium-223 (223Ra) was the first radioactive isotope approved for treating
castration-resistant prostate cancer (CRPC) with symptomatic bone metastases without
visceral metastatic disease. To better understand the action of 223Ra, its role in the tumor
microenvironment represents a crucial aspect. A literature search was conducted using
the PubMed/MEDLINE database and studies regarding the relationship between 223Ra
and the tumoral microenvironment were considered. The tumoral microenvironment is a
complex setting in which complex interactions between cells and molecules occur. Radium223, as an alpha-emitter, induces double-stranded DNA breaks; to potentiate this effect, it
could be used in patients with genetic instability but also in combination with therapies
which inhibit DNA repair, modulate the immune response, or control tumor growth. In
conclusion, a few studies have taken into consideration the tumoral microenvironment in
association with 223Ra. However, its understanding is a priority to better comprehend how
to effectively exploit 223Ra and its action mechanism
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