The term chondrosarcoma refers to a rare and heterogeneous group of malignant cartilaginous tumors that are typically resistant to chemotherapy and radiotherapy. Metastatic chondrosarcoma has a poor prognosis, and effective systemic therapies are lacking. Isocitrate dehydrogenase (IDH) mutations represent a potential therapeutic target, but IDH inhibitors alone have shown limited clinical efficacy to date. Although the role of conventional chemotherapy is still subject to debate, some evidence suggests it may provide therapeutic benefits in advanced cases. In this study, we aimed to identify effective compounds for combination therapy in chondrosarcoma. Using high-throughput screening, we evaluated a panel of anticancer agents in IDH1-mutant chondrosarcoma cell lines and their mutant IDH1 knockout derivatives. The top 20 most potent compounds were identified across all cell lines, irrespective of IDH mutation status. Representative drugs selected for further investigation included docetaxel, methotrexate, panobinostat, idarubicin, camptothecin, and pevonedistat. These drugs inhibited colony formation, induced apoptosis and cell cycle arrest, and exhibited synergistic antitumor activity in two-drug combinations. In conclusion, we identified several highly effective agents with potent anti-tumor activity in chondrosarcoma cells, independent of IDH mutation status. These agents represent promising candidates for chondrosarcoma therapy and warrant further preclinical investigation and potential inclusion in clinical trials.

Background. Establishing prompt vascular access facilitates resuscitation for out-of-hospital cardiac arrest (OHCA). While intraosseous access may decrease the time to vascular access, the impact on clinical outcomes in OHCA is unclear. Therefore, we aim to compare the effect of intraosseous (IO) versus intravenous (IV) vascular access on clinical outcomes after OHCA resuscitation. Methods. A systematic review and meta-analysis were performed to synthesize evidence from randomized controlled trials (RCTs) obtained from PubMed, CENTRAL, Scopus, and Web of Science until January 2025. Using Stata MP v. 17, we used the fixed-effects model to report dichotomous outcomes using the risk ratio (RR) and continuous outcomes using the mean difference (MD) with a 95% confidence interval (CI). PROSPERO ID: CRD42024627354. Results. Four RCTs and 9475 patients were included. There was no difference between both groups regarding the prehospital return of spontaneous circulation (ROSC) (RR: 0.97, 95% CI [0.91, 1.03], p = 0.33), maintained ROSC (RR: 0.94, 95% CI [0.87, 1.01], p = 0.09), survival to discharge (RR: 1.03 with 95% CI [0.88, 1.21], p = 0.71), 30-day survival (RR: 0.98, 95% CI [0.82, 1.17], p = 0.79), or favorable neurological recovery (RR: 1.07, 95% CI [0.90, 1.29], p = 0.44). However, IO access significantly increased first-attempt access (RR: 1.24, 95% CI [1.19, 1.29], p < 0.001), decreased time to vascular access (MD: −0.24 min with 95% CI [−0.48, −0.01], p = 0.04), and decreased time to drug administration (MD: −0.38, 95% CI [−0.66, −0.10], p = 0.01). Conclusions. IO and IV vascular accesses showed similar clinical outcomes in OHCA patients, with no difference in ROSC, survival, or neurological recovery. Still, IO access showed a better procedural outcome with increased first-attempt success rates, faster access, and faster drug administration.