Treatment with Pexa-Vec Daporinad research buy was generally well-tolerated in patients with advanced HCC when administered by IV infusion and/or IT injection. The majority of patients generally adhere to the schedule of multiple injections. Further studies with Pexa-Vec IT and IV are warranted in this indication.
Disclosures: Caroline Breitbach – Employment: Jennerex Biotherapeutics Jeong Heo – Grant/Research Support: Jennerex, Green Cross Riccardo Lencioni – Consulting: Jennerex Inc.; Speaking and Teaching: Bayer Healthcare Tae-Ho Hwang – Grant/Research Support: Jennerex James Burke – Employment: Jennerex The following people have nothing to disclose: Mong Cho Hepatocellular carcinoma (HCC) is the sixth most common cancer with high fatality and mortality worldwide. The rapid development of drug resistance to current chemotherapies and targeted therapies has hindered the effectiveness of HCC treatments, leading to a poor prognosis for HCC patients. Recently, we identified a potential mechanism that how HCC obtains drug resistance against Sorafenib through Pregnane X receptor (PXR)
pathway. PXR is a nuclear receptor that senses the presence of foreign toxic substances including drugs and up-regu-lates the expression of proteins involved in drug metabolism, detoxification and clearance process. Surface plasmon resonance (SPR) has demonstrated that Sorafenib exhibits high affinity to PXR, functions as PXR’s ligand, and triggers 上海皓元医药股份有限公司 gene transcriptions/translations that are necessary for drug detoxification and clearance, leading to tolerance. Our results showed Panobinostat solubility dmso that Sorafenib promoted accumulation of PXR in nucleus and recruitment of PXR to the promoter region of multi drug resistance (MDR). Further results from Luciferase
and Western blot assays showed that Sorafenib induced the transcription and translation of PXR downstream genes including MDR and CYP3A4 in a dose dependent manner. In addition, down-regulation of PXR expression by siRNA blocked Sorafenib-associated up-regulation of MDR and CYP3A4. On the other hand, up-regulation of PXR activity induced by Anisomycin significantly reduced the inhibitory effect of Sorafenib on HepG2 cell proliferation. In conclusion, our study indicates a novel molecular mechanism that drug resistance against Sorafenib in HCC is mediated by PXR activation and PXR downstream gene transcription/translation, offering a potential to target the drug resistance pathway and improve future HCC’s treatment outcome. Disclosures: The following people have nothing to disclose: Yin Ying Lu, Fan Feng, Fan Zhang, Xudong Gao, Chunping Wang, Xiujuan Chang, Jianhui Qu, Hong Wang, Zhen Zeng, Mingliang Cheng, Chunzhang Yang, Yongping Yang