Bone_metastases_in_advanced_prostate_cancer___Dondossola-sc-5242
Bone_metastases_in_advanced_prostate_cancer___Dondossola
Bone metastases are a major complication in patients with advanced prostate cancer (PCa), with limited therapeutic options. Targeting the bone environment has recently resulted in the approval of radium-223 (Ra223), a new life-prolonging therapy for patients with advanced metastatic PCa. This alpha-emitter, endowed with chemical properties similar to calcium, localizes in bone and displays a highly energetic ionizing radiation whit limited penetrance. As a consequence, the high-linear energy transfer radiation mainly induces non-reparable DNA double-strand breaks, followed by cell death. Despite significantly increasing symptom free and overall survival, Rad223 did not proportionally reduce serum PSA concentration, but it decreased alkaline phosphatase levels, suggesting a major effect on the microenvironment. The purpose of this research is to dissect Rad223 therapeutic outcome. As part of this effort, mice were implanted with human PC3 PCa cells in the tibia and treated with 385 KBeq/Kg Rad223. PC3-bearing bones and control bones were recovered 2 and 8 days post-treatment and processed for RNA Seq. So, samples with PC3 are mixed human and mouse, samples without PC3 are mouse only.  (The experiment was performed at the end of July, so Rad223 underwent through about 21 decays. No radioactivity is present in the samples anymore).
Bone metastases are a major complication in patients with advanced prostate cancer (PCa), with limited therapeutic options. Targeting the bone environment has recently resulted in the approval of radium-223 (Ra223), a new life-prolonging therapy for patients with advanced metastatic PCa. This alpha-emitter, endowed with chemical properties similar to calcium, localizes in bone and displays a highly energetic ionizing radiation whit limited penetrance. As a consequence, the high-linear energy transfer radiation mainly induces non-reparable DNA double-strand breaks, followed by cell death. Despite significantly increasing symptom free and overall survival, Rad223 did not proportionally reduce serum PSA concentration, but it decreased alkaline phosphatase levels, suggesting a major effect on the microenvironment. The purpose of this research is to dissect Rad223 therapeutic outcome. As part of this effort, mice were implanted with human PC3 PCa cells in the tibia and treated with 385 KBeq/Kg Rad223. PC3-bearing bones and control bones were recovered 2 and 8 days post-treatment and processed for RNA Seq. So, samples with PC3 are mixed human and mouse, samples without PC3 are mouse only.  (The experiment was performed at the end of July, so Rad223 underwent through about 21 decays. No radioactivity is present in the samples anymore).