Medicine and Health Sciences Commons^™

Cabozantinib Plus Atezolizumab In Previously Untreated Advanced Hepatocellular Carcinoma And Previously Treated Gastric Cancer And Gastroesophageal Junction Adenocarcinoma: Results From Two Expansion Cohorts Of A Multicentre, Open-Label, Phase 1b Trial (Cosmic-021)., Daneng Li, Yohann Loriot, Adam Burgoyne, James Cleary, Armando Santoro, Daniel Lin, Santiago Ponce Aix, Ignacio Garrido-Laguna, Ramu Sudhagoni, Xiang Guo, Svetlana Andrianova, Scott Paulson

Kimmel Cancer Center Faculty Papers

BACKGROUND: Cabozantinib is approved for previously treated advanced hepatocellular carcinoma (aHCC) and has been investigated in gastric cancer (GC) and gastroesophageal junction adenocarcinoma (GEJ). Atezolizumab plus bevacizumab is approved for unresectable or metastatic HCC untreated with prior systemic therapy. We evaluated efficacy and safety of cabozantinib plus atezolizumab in aHCC previously untreated with systemic anticancer therapy or previously treated GC/GEJ.

METHODS: COSMIC-021 (ClinicalTrials.gov, NCT03170960) is an open-label, phase 1b study in solid tumours with a dose-escalation stage followed by tumour-specific expansion cohorts, including aHCC (cohort 14) and GC/GEJ (cohort 15). Eligible patients were aged ≥18 years with measurable locally advanced, …

Discovery Of A New Cdk4/6 And Pi3k/Akt Multiple Kinase Inhibitor Aminoquinol For The Treatment Of Hepatocellular Carcinoma., Zhong-Kun Xia, Wei Wang, Jian-Ge Qiu, Xi-Nan Shi, Hong-Jian Li, Rong Chen, Kun-Bin Ke, Chao Dong, Ying Zhu, Shi-Guo Wu, Rong-Ping Zhang, Zhuo-Ran Meng, Hui Zhao, Peng Gu, Kwong-Sak Leung, Man-Hon Wong, Xiao-Dong Liu, Feng-Mei Zhou, Jian-Ying Zhang, Ya-Ting Yao, Si-Jia Wang, Chun-Yang Zhang, Yan-Ru Qin, Marie Chia-Mi Lin, Bing-Hua Jiang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: Hepatocellular carcinoma (HCC) is a lethal malignancy lacking effective treatment. The Cyclin-dependent kinases 4/6 (CDK4/6) and PI3K/AKT signal pathways play pivotal roles in carcinogenesis and are promising therapeutic targets for HCC. Here we identified a new CDK4/6 and PI3K/AKT multi-kinase inhibitor for the treatment of HCC.

Methods: Using a repurposing and ensemble docking methodology, we screened a library of worldwide approved drugs to identify candidate CDK4/6 inhibitors. By MTT, apoptosis, and flow cytometry analysis, we investigated the effects of candidate drug in reducing cell-viability,inducing apoptosis, and causing cell-cycle arrest. The drug combination and thermal proteomic profiling (TPP) method were …

Hepatocellular Carcinoma Treated With Microwave Ablation Prior To Liver Transplantation, Nicole Wagner, Amanda Smolock, Michael Markovitz, Varun Danda, Christopher Neely, Warren Maley, Jesse Civan, Colette Shaw

Phase 1

Introduction: Ablation is a minimally invasive procedure that limits local liver tumor progression and prolongs patients’ transplantation eligibility. Microwave ablation (MWA) utilizes higher temperatures than the standard of care, radiofrequency ablation (RFA), which increases efficiency. Meta-analyses compared MWA with RFA for the treatment of HCC and showed similar efficacy and safety between these modalities. However, limited pathologic data exists determining whether explanted tumors remained viable after MWA.

Methods: Our database was reviewed retrospectively for patients with HCC who underwent MWA prior to liver transplantation between 2013 and 2019. Patient demographics, etiology of disease, tumor size, procedure details, bilirubin, MELD, …

Ferritin Level Prospectively Predicts Hepatocarcinogenesis In Patients With Chronic Hepatitis B Virus Infection, Zhenyuan Bian, Hie-Won Hann, Zhong Ye, Chun Yin, Yang Wang, Wan Fang, Shaogui Wan, Chun Wang, Kaishan Tao

Department of Medical Oncology Faculty Papers

Previous studies have detected a higher level of ferritin in patients with hepatocellular carcinoma (HCC), but a potential causal association between serum ferritin level and hepatocarcinogenesis remains to be clarified. Using a well-established prospective cohort and longitudinally collected serial blood samples, the association between baseline ferritin levels and HCC risk were evaluated in 1,152 patients infected with hepatitis B virus (HBV), a major risk factor for HCC. The association was assessed by Cox proportional hazards regression model using univariate and multivariate analyses and longitudinal analysis. It was demonstrated that HBV patients who developed HCC had a significantly higher baseline ferritin …

Tnfα Induces Ca2+ Influx To Accelerate Extrinsic Apoptosis In Hepatocellular Carcinoma Cells, Jianjun Zhu, Mingpeng Jin, Jiaojiao Wang, Hui Zhang, Yousheng Wu, Deyang Li, Xiaoying Ji, Hushan Yang, Chun Yin, Tingting Ren, Jinliang Xing

Department of Medical Oncology Faculty Papers

BACKGROUND: Tumor necrosis factor-α has been proven an effective anticancer agent in preclinical studies. However, the translation of TNFα from research to clinic has been blocked by significant systemic toxicity and limited efficacy at maximal tolerated dose, which need urgently to be solved.

METHODS: The level of cytosolic Ca

RESULTS: Here, we demonstrated that TNFα induced extracellular Ca

CONCLUSIONS: Our study provides the evidence supporting a novel mechanism by which TNFα induces extracellular Ca