Abstract 6852: Targeted administration of lactate dehydrogenase inhibitor during transarterial of hepatocellular cardinomas in a rat model
Authors: Ryan Baron, Ariful Islam, George McClung, Ryan El Ghazal, Nicholas Perkons, Alexey Gurevich, Jennifer Crainic, Daniel Ackerman, Nicolas Skuli, Gregory Nadolski, Stephen Hunt, Terence Gade
Journal: Cancer Research (2025)

Abstract Introduction: Despite improvements in locoregional therapy, recurrence of hepatocellular carcinoma (HCC) remains common, as tumor cells can respond to therapy by undergoing metabolic reprogramming to utilize anaerobic glycolytic pathways via lactate dehydrogenase. In this work, we assessed the growth rates and recurrence rates of HCC in target tumors undergoing transarterial embolization (TAE) with an LDH inhibitor (LDHi), bland TAE (BLAND), and sham therapy (SHAM). Methods and Materials: Development of autochthonous HCC was induced in 25 Wistar rats using DEN and tumor progressions were tracked with serial MRI until the target tumor reached a volume of 100-300 mm3. TAE with LDHi were performed using sequential administration of 10 µg/kg LDHi followed by 40-120 µm Embosphere (Merit Medical Systems) (n=13), while bland TAE were performed using Embosphere alone(n=8). An additional cohort underwent a sham TAE procedure without the administration of Embosphere (n=4). Following surgery, rats were serially imaged using T2 MRI, where tumor growth was tracked and monitored for treatment response and potential recurrence. Rats were classified as progressive disease (PD) if there was no decrease in tumor volume by &amp;lt;20%, PR if tumor volume decreased by &amp;gt;20%, and CR if the tumor was eradicated. Recurrence following PR was classified by a &amp;gt;20% increase in tumor volume from the lowest post-treatment volume. Results: LDHi target tumors had an average %change in tumor volume of -64% from treatment volume, while the BLAND showed a -38% decrease (p=0.068). Results of a Kaplan-Meier survival analysis with a log-rank test showed a significant difference in survival between the groups (p=0.006). All SHAM rats showed no response to treatment and were classified as PD. Treatment responses in the BLAND cohort were2/8 PD and 6/8 PR, while responses in the LDHi cohort were 1/13 PD, 11/13 PR, and1/13 CR. All rats classified as PR experienced recurrence and the time of progression free survival was significantly longer in the LDHi cohort (24 days) as compared to the BLAND (13 days) (p = 0.036). Conclusion: Administration of LDHi during TAE yields a larger decrease in targeted tumor volume as compared to BLAND TAE, while also providing a statistically significant improvement in progression free survival. Citation Format: Ryan Baron, Ariful Islam, George McClung, Ryan El Ghazal, Nicholas Perkons, Alexey Gurevich, Jennifer Crainic, Daniel Ackerman, Nicolas Skuli, Gregory Nadolski, Stephen Hunt, Terence Gade. Targeted administration of lactate dehydrogenase inhibitor during transarterial of hepatocellular cardinomas in a rat model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6852.