Abstract 3927: Bone Metastasis Technology Platform: Establishing clinically relevant bone metastasis models for breast and prostate cancer and multiple myeloma
Authors: Tiina E. Kähkönen, Jie Wen, Ru Yang, Yuyang Xu, Michael Zhang, Jussi M. Halleen
Journal: Cancer Research (2025)

Bone metastases are a significant clinical problem in many major cancers, especially in breast and prostate cancer where 70-90% of advanced patients develop bone metastases. Myeloma bone disease is associated with similar clinical problems than bone metastases, including increased risk of fractures and bone pain that decrease the quality of life. Current cancer therapies can only partially decrease tumor growth, resulting in only 5% of bone metastatic patients being alive 5 years after the diagnosis. Bone metastases are therefore a high unmet medical need with a high demand for effective therapies. Lack of appropriate preclinical bone metastasis models that would exhibit the same clinical features that are observed in bone metastatic patients has made it difficult to advance therapy development at early stages. This study describes the establishment of three preclinical bone metastasis models, a breast cancer model using 4T1 mouse triple-negative breast cancer cells in BALB/c mice, a prostate cancer model using RM-1 mouse androgen-insensitive prostate cancer cells in C57BL/6 mice, and a multiple myeloma model using human RPMI 8226 cells in immunodeficient NPG mice. The cancer cells were inoculated intratibially into the bone marrow to model tumor growth in bone. Tumor growth was monitored by bioluminescence imaging (BLI), cancer-induced bone changes by X-ray imaging, and bone pain by Von Frey filaments (mechanical allodynia). In the 4T1 breast cancer model, 100% of the mice had bone metastases at day 7, and maximum study duration was 21 days. Osteolytic bone lesions were clearly observed and bone pain was detected at day 7. In the RM-1 prostate cancer model, 83% of the mice had bone metastases at day 7, and 100% of the mice at day 14, and maximum study duration was 28 days. Bone pain was observed at day 7, and osteolytic-mixed bone metastases were visible at day 14. In the RPMI 8226 multiple myeloma model, 100% tumor take rate was detected at day 7. Osteolytic bone metastases were visible at day 21, and maximum study duration was 100 days. We have established a clinically relevant Bone Metastasis Technology Platform (BMTP©) that currently includes preclinical bone metastasis models for breast and prostate cancer and multiple myeloma. These models have clinical features that are similar to those observed in bone metastatic patients. In preclinical models established in BMTP, tumor burden is monitored by BLI, the type and extent of cancer-induced bone loss is visualized by X-ray imaging, and bone pain is analyzed to provide a clinically relevant readout about the quality of life. We conclude that BMTP is a clinically relevant translational tool for evaluating efficacy of cancer therapies on bone metastasizing cancers. Citation Format: Tiina E. Kähkönen, Jie Wen, Ru Yang, Yuyang Xu, Michael Zhang, Jussi M. Halleen. Bone Metastasis Technology Platform: Establishing clinically relevant bone metastasis models for breast and prostate cancer and multiple myeloma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3927.