Table 1.
The main findings of radium-223 in nonclinical cancer studies.
| Authors | Year | Nonclinical Model | Main Findings | Ref |
|---|---|---|---|---|
| Henriksen et al. | 2002 | MT-1 human breast cancer bone metastasis model in rats | Radium-223 increases symptom-free survival. | [13] |
| Larsen et al. | 2006 | BALB/c mice | Doses ten-fold higher than therapeutic doses do not cause complete bone marrow suppression. | [77] |
| Suominen et al. | 2013 | MDA-MB-231 human breast cancer bone metastasis model in mice | Radium-223 prevents tumor-induced cachexia, decreases osteolysis, induces DNA DSBs, and extends survival alone and in combination with zoledronic acid or doxorubicin. | [15] |
| Malamas et al. | 2016 | In vitro | Radium-223 significantly enhances T cell-mediated lysis of prostate, breast, and lung carcinoma tumor cells by CD8+ cytotoxic T lymphocytes. | [78] |
| Suominen et al. | 2017 | 5TGM1 mouse myeloma model | Combination of radium-223 with bortezomib could constitute a novel, effective therapy for multiple myeloma. | [79] |
| Suominen et al. | 2017 | LNCaP, LuCaP 58 prostate cancer bone growth models in mice | Radium-223 inhibits tumor growth, tumor-induced osteoblastic bone growth, and protects normal bone architecture. Radium-223 shows a preferential uptake in bone lesions compared to normal bone and deposits in newly formed intratumoral bone matrix. Radium-223 induces DBS in local tumor cells, OBs and OCs. |
[16] |
| Wengner et al. | 2018 | LNCaP human prostate cancer bone growth model in mice | Treatment with ATR inhibitor BAY 1895344 and radium-223 exhibits synergistic antitumor activity. | [80] |
| Wickstroem et al. | 2018 | OVCAR-3 ovarian cancer model in mice | MSLN-TTC increases the antitumor efficacy of ATR and PARP inhibitors. | [81] |
| Dondossola et al. | 2019 | PC3 and C4–2B human PCa cell lines in mouse bones | Micro-tumors showed good response to radium-223. Larger tumor areas were not as efficiently controlled by radium-223. | [82] |
| Bannik et al. | 2019 | In vitro | Synergistic in vitro effects were observed when radium-223 was combined with the ATR inhibitor BAY 1895344. | [83] |
| Hagemann et al. | 2019 | In vitro | MSLN-TTC is able to induce immunogenic cell death and secretion of pro-inflammatory cytokines in vitro. | [84] |