Differential responses to 223 Ra and Alpha-particles exposure in prostate cancer driven by mitotic catastrophe.

Autor: Guerra Liberal FDC; The Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, United Kingdom., Moreira H; The Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, United Kingdom., Redmond KM; The Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, United Kingdom., O'Sullivan JM; The Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, United Kingdom.; Northern Ireland Cancer Centre, Belfast Health and Social Care Trust, Belfast, United Kingdom., Alshehri AHD; The Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, United Kingdom.; Department of Radiological Sciences, College of Applied Medical Sciences, Najran University, Najran, Saudi Arabia., Wright TC; The Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, United Kingdom., Dunne VL; The Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, United Kingdom., Campfield C; Northern Ireland Cancer Centre, Belfast Health and Social Care Trust, Belfast, United Kingdom., Biggart S; Northern Ireland Cancer Centre, Belfast Health and Social Care Trust, Belfast, United Kingdom., McMahon SJ; The Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, United Kingdom., Prise KM; The Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, United Kingdom.
Jazyk: angličtina
Zdroj: Frontiers in oncology [Front Oncol] 2022 Jul 28; Vol. 12, pp. 877302. Date of Electronic Publication: 2022 Jul 28 (Print Publication: 2022).
DOI: 10.3389/fonc.2022.877302
Abstrakt: Introduction: Radium-223 ( 223 Ra) has been shown to have an overall survival benefit in metastatic castration-resistant prostate cancer (mCRPC) involving bone. Despite its increased clinical usage, relatively little is known regarding the mechanism of action of 223 Ra at the cellular level.
Methods: We evaluated the effects of 223 Ra irradiation in a panel of cell lines and then compared them with standard X-ray and external alpha-particle irradiation, with a particular focus on cell survival and DNA damage repair kinetics.
Results: 223 Ra exposures had very high, cell-type-dependent RBE 50% ranging from 7 to 15. This was significantly greater than external alpha irradiations (RBE 50% from 1.4 to 2.1). These differences were shown to be partially related to the volume of 223 Ra solution added, independent of the alpha-particle dose rate, suggesting a radiation-independent mechanism of effect. Both external alpha particles and 223 Ra exposure were associated with delayed DNA repair, with similar kinetics. Additionally, the greater treatment efficacy of 223 Ra was associated with increased levels of residual DNA damage and cell death by mitotic catastrophe.
Conclusions: These results suggest that 223 Ra exposure may be associated with greater biological effects than would be expected by direct comparison with a similar dose of external alpha particles, highlighting important challenges for future therapeutic optimization.
Competing Interests: JO’S has received honoraria as part of the speakers’ bureau and the advisory board of Bayer and has received institutional research funding from Bayer. KP has received speaker honoraria from Bayer. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Guerra Liberal, Moreira, Redmond, O’Sullivan, Alshehri, Wright, Dunne, Campfield, Biggart, McMahon and Prise.)
Databáze: MEDLINE
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