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Review
. 2025 Feb 12;13(2):456.
doi: 10.3390/biomedicines13020456.

The Tight Relationship Between the Tumoral Microenvironment and Radium-223

Miriam Conte  1 , Miriam Tomaciello  1 , Maria Silvia De Feo  1 , Viviana Frantellizzi  1 , Francesco Marampon  1 , Flaminia De Cristofaro  1 , Giuseppe De Vincentis  1 , Luca Filippi  2
Affiliations
Review

The Tight Relationship Between the Tumoral Microenvironment and Radium-223

Miriam Conte et al. Biomedicines. .

Abstract

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. Radium-223, 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.

Keywords: BRCA; PARP; abiraterone; alpha-emitter; chemotherapy; hormonal therapy; osteoblasts; prostate cancer; radium-223; tumor microenvironment.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Schematic representation of the “seed and soil” theory. From right to left: primary tumor with tumor cells detaching, migrating through the vascular system, and attracting of circulating tumor cells (CTCs) through the interaction between the CXCR4 receptor and the CXCL12 ligand released by osteoblasts and stimulation by angiopoietin (Ang-1) and osteopontin (OPN), prompting the CTCs to enter the bone (the CTCs become disseminating tumor cells (DTCs)), leading to the formation of a “pre-metastatic niche”. Figure was drawn using pictures from servier medical art. Servier medical art by servier is licensed under a creative CommonsAttribution 3.0 unported license (https://creativecommons.Org/licenses/by/3.0/ accessed on 8 February 2025).
See this image and copyright information in PMC

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