Radiation-Induced Remodeling of Bone Metastases and the Bone Marrow Microenvironment: From External-Beam Radiotherapy to Radiopharmaceutical Therapy
5 affiliations
- 1Department of Radiation Science, Graduate School of Health Sciences, Hirosaki University, Hirosaki 036-8564, Japan
- 2Research Center for Biomedical Sciences, Hirosaki University Graduate School of Health Sciences, Hirosaki 036-8564, Japan
- 3Department of Nursing, Faculty of Medical Technology, Teikyo University, Tokyo 173-8605, Japan
- 4Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE-10691 Stockholm, Sweden
- 5Department of Radiology, Aomori Rosai Hospital, Hachinohe 031-8551, Japan
Abstract
Background/Objectives: Bone metastases arise within a specialized microenvironment in which tumor cells interact with skeletal, stromal, vascular, immune, and hematopoietic compartments. Radiotherapy therefore affects not only metastatic tumor cells but also the surrounding bone and marrow niches. This review examines radiation-induced remodeling of the bone metastatic and bone marrow microenvironments across external-beam radiotherapy (EBRT) and radiopharmaceutical therapy (RPT). Methods: We performed a narrative synthesis of experimental and clinical studies addressing cellular radiosensitivity, skeletal and stromal remodeling, hematopoietic injury, vascular and immune responses, oxidative and metabolic stress, and spatial and temporal patterns of radiation delivery. Emerging transcriptomic, proteomic, metabolomic, lipidomic, single-cell, and spatial approaches were also considered. Results: EBRT and RPT produce overlapping but biologically distinct perturbations because of differences in dose rate, exposure duration, particle range, target localization, microscopic energy deposition, and spatial dose heterogeneity. These differences can influence tumor control, resistance, bone remodeling, and marrow toxicity through effects on osteoblasts, osteoclasts, stromal and vascular cells, immune populations, and HSPCs. These issues are particularly relevant to metastatic castration-resistant prostate cancers, in which bone seeking and tumor targeting radiopharmaceuticals differentially irradiate cellular compartments within the same skeletal environment. Conclusions: Bone metastases should be viewed as part of a dynamic bone–tumor–marrow microenvironment. Integrating radiation biology, spatial dosimetry, and multi-omics may support more individualized treatment strategies that maximize tumor control while limiting skeletal and hematologic injury.
Related
- Conserved Metastatic Cell States and Spatial Immune Microenvironment Remodeling Define Pancreatic Cancer Liver Metastases
- 644 Combining radiopharmaceutical ligand therapy with CAR T cells to overcome the heterogeneous immunosuppressive prostate tumor microenvironment
- A conditional, myeloid-cell specific estrogen receptor α deletion reprograms the liver immune microenvironment and impedes the growth of colon carcinoma liver metastases
- Incremental Value of Radiation Dose for Prognostic Stratification Beyond Performance Status in Palliative Radiation Therapy for Bone Metastases
- Efficacy and safety of narlumosbart in combination with stereotactic body radiation therapy followed by first-line chemotherapy combined with immunotherapy in advanced driver gene-negative non-small cell lung cancer patients with bone metastases: a phase II, single-arm, single-centre clinical trial protocol
BibTeX
@article{monzen2026radiationinduced,
title = {{Radiation-Induced Remodeling of Bone Metastases and the Bone Marrow Microenvironment: From External-Beam Radiotherapy to Radiopharmaceutical Therapy}},
author = {Satoru Monzen and Akihito Kotani and Masaki Tatara and Atsushi Muro and Yasuyo Fukushi and Andrzej Wojcik and Yasushi Mariya},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18213500},
url = {https://www.mdpi.com/2072-6694/18/21/3500},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Radiation-Induced Remodeling of Bone Metastases and the Bone Marrow Microenvironment: From External-Beam Radiotherapy to Radiopharmaceutical Therapy
AU - Satoru Monzen
AU - Akihito Kotani
AU - Masaki Tatara
AU - Atsushi Muro
AU - Yasuyo Fukushi
AU - Andrzej Wojcik
AU - Yasushi Mariya
PY - 2026
DA - 2026/10/30
JO - Cancers
DO - 10.3390/cancers18213500
UR - https://www.mdpi.com/2072-6694/18/21/3500
AB - Background/Objectives: Bone metastases arise within a specialized microenvironment in which tumor cells interact with skeletal, stromal, vascular, immune, and hematopoietic compartments. Radiotherapy therefore affects not only metastatic tumor cells but also the surrounding bone and marrow niches. This review examines radiation-induced remodeling of the bone metastatic and bone marrow microenvironments across external-beam radiotherapy (EBRT) and radiopharmaceutical therapy (RPT). Methods: We performed a narrative synthesis of experimental and clinical studies addressing cellular radiosensitivity, skeletal and stromal remodeling, hematopoietic injury, vascular and immune responses, oxidative and metabolic stress, and spatial and temporal patterns of radiation delivery. Emerging transcriptomic, proteomic, metabolomic, lipidomic, single-cell, and spatial approaches were also considered. Results: EBRT and RPT produce overlapping but biologically distinct perturbations because of differences in dose rate, exposure duration, particle range, target localization, microscopic energy deposition, and spatial dose heterogeneity. These differences can influence tumor control, resistance, bone remodeling, and marrow toxicity through effects on osteoblasts, osteoclasts, stromal and vascular cells, immune populations, and HSPCs. These issues are particularly relevant to metastatic castration-resistant prostate cancers, in which bone seeking and tumor targeting radiopharmaceuticals differentially irradiate cellular compartments within the same skeletal environment. Conclusions: Bone metastases should be viewed as part of a dynamic bone–tumor–marrow microenvironment. Integrating radiation biology, spatial dosimetry, and multi-omics may support more individualized treatment strategies that maximize tumor control while limiting skeletal and hematologic injury.
SN - 2072-6694
ER -