Synergistic Activity of DNA Damage Response Inhibitors in Combination with Radium-223 in Prostate Cancer.

Radium-223 (Ra) and Lutetium-177-labelled-PSMA-617 (Lu-PSMA) are currently the only radiopharmaceutical treatments to prolong survival for patients with metastatic-castration-resistant prostate cancer (mCRPC); however, mCRPC remains an aggressive disease. Recent clinical evidence suggests patients with mutations in DNA repair genes associated with homologous recombination have a greater clinical benefit from Ra. In this study, we aimed to determine the utility of combining DNA damage response (DDR) inhibitors to increase the therapeutic efficacy of X-rays, or Ra.

Characterization of Intrinsic Radiation Sensitivity in a Diverse Panel of Normal, Cancerous and CRISPR-Modified Cell Lines.

Intrinsic radiosensitivity is a major determinant of radiation response. Despite the extensive amount of radiobiological data available, variability among different studies makes it very difficult to produce high-quality radiosensitivity biomarkers or predictive models. Here, we characterize a panel of 27 human cell lines, including those derived from lung cancer, prostate cancer, and normal tissues.

Modulating the unfolded protein response with ONC201 to impact on radiation response in prostate cancer cells.

Prostate cancer (PCa) is the most common non-cutaneous cancer in men and a notable cause of cancer mortality when it metastasises. The unfolded protein response (UPR) can be cytoprotective but when acutely activated can lead to cell death. In this study, we sought to enhance the acute activation of the UPR using radiation and ONC201, an UPR activator.

Computational modeling of radiobiological effects in bone metastases for different radionuclides.

Purpose: Computational simulation is a simple and practical way to study and to compare a variety of radioisotopes for different medical applications, including the palliative treatment of bone metastases. This study aimed to evaluate and compare cellular effects modelled for different radioisotopes currently in use or under research for treatment of bone metastases using computational methods.

Methods: Computational models were used to estimate the radiation-induced cellular effects (Virtual Cell Radiobiology algorithm) post-irradiation with selected particles emitted by Strontium-89 (Sr), Samarium-153 (Sm), Lutetium-177 (Lu), and Radium-223 (Ra).