Abstract
New therapeutic approaches are needed to improve patient outcomes. Traditional pyrimidine antimetabolic chemotherapy agents like 5-FU and capecitabine face challenges of resistance, toxicity, and variability in patient response. CLX-155A, a novel oral prodrug, aims to enhance chemotherapy efficacy by combining 5-fluorouracil (5-FU) and valproic acid (VPA) to utilize synergistic mechanisms. This preclinical study addresses the research question: What is CLX-155A's preclinical activity in nude mouse models of triple-negative breast cancer (TNBC)?
This study assesses the anticancer efficacy of CLX-155A in TNBC nude xenograft mouse models, focusing on tumor growth inhibition and its potential effects when combined with paclitaxel. Mice inoculated with cancer cells were treated with CLX-155A at 1000 mg/kg/D either as monotherapy or in combination with paclitaxel at 15mg/kg daily. The study utilized comparisons with vehicle and capecitabine at 1000 mg/kg/D. The primary endpoint was tumor growth rate (%). Secondary assessments included survival and weight loss.
CLX-155A displayed significant antitumor activity in a TNBC model. The two CLX-155A groups (CLX-155A at 1000 mg/kg and CLX-155A at 1000 mg/kg + paclitaxel at 15 mg/kg) showed a significant effect (p<0.001) versus the vehicle control. At equal dosages to capecitabine, CLX-155A showed similar effects. It was numerically superior compared to capecitabine at equal dosages, both alone and in combination with paclitaxel. Further, CLX-155A as monotherapy showed similar effects to capecitabine with paclitaxel at 15mg/kg daily.
Overall, CLX-155A exhibits promising preclinical efficacy in CRC and TNBC models. Due to its dual-action mechanism, it may offer potential advantages over existing therapies. Additional studies are warranted to explore its clinical potential further and optimize dosing strategies.