A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Darolutamide in Combination with Radium-223 Exhibits Synergistic Antitumor Efficacy in LNCaP Prostate Cancer Models
Tekijät: Hagemann, Urs B.; Schatz, Christoph A.; Suominen, Mari I.; Schlicker, Andreas; Knuuttila, Matias; Wilson, Timothy; Alhoniemi, Esa; Käkönen, Sanna-Maria; Haendler, Bernard; Scholz, Arne
Kustantaja: MDPI
Kustannuspaikka: BASEL
Julkaisuvuosi: 2024
Journal: International Journal of Molecular Sciences
Tietokannassa oleva lehden nimi: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Lehden akronyymi: INT J MOL SCI
Artikkelin numero: 13672
Vuosikerta: 25
Numero: 24
Sivujen määrä: 14
ISSN: 1661-6596
eISSN: 1422-0067
DOI: https://doi.org/10.3390/ijms252413672
Verkko-osoite: https://doi.org/10.3390/ijms252413672
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/484694099
Despite treatment, prostate cancer commonly progresses into castration-resistant prostate cancer (CRPC), which remains largely incurable, requiring the development of new interventions. Darolutamide is an orally administered second-generation androgen receptor inhibitor indicated for patients with non-metastatic CRPC or metastatic hormone-sensitive prostate cancer. Here, we evaluated the effect of androgen receptor (AR) inhibition by darolutamide in combination with DNA double-strand-break-inducing targeted radium-223 alpha therapy in vitro and in an intratibial LNCaP xenograft model mimicking prostate cancer metastasized to bone. The results highlight the synergistic antitumor efficacy of darolutamide in combination with radium-223 both in vitro and in vivo. This effect was most likely driven by the downregulation of genes involved in DDR signaling, which was demonstrated in vitro by a gene set enrichment analysis. The combination treatment also reduced pathological tumor-induced effects in bone by decreasing the number of osteoblasts and osteoclasts and reducing abnormal bone formation in tumor-bearing bone. Additionally, it was shown that darolutamide does not affect the uptake of radium-223 into bone tissue. These results support the investigation of darolutamide in combination with radium-223 for the treatment of patients with CRPC metastasized to bone.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
Julkaisussa olevat rahoitustiedot:
Bayer AG paid Pharmatest to perform the experiments. Darolutamide is jointly developed by Bayer AG and Orion Corporation (Espoo, Finland). Aurexel Life Sciences Ltd. ( www.aurexel.com ) is acknowledged for editorial support funded by Bayer AG.
