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Molecular targeted therapy for advanced hepatocellular carcinoma: current status and future perspectives

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Abstract

Sorafenib, a multikinase inhibitor targeting vascular endothelial growth factor (VEGF)-mediated angiogenesis, is the first drug found to prolong survival of patients with advanced hepatocellular carcinoma (HCC). This advance has shifted the paradigm of systemic treatment for HCC toward molecular targeted therapy (MTT). However, the disease-stabilizing effect of VEGF signaling-targeted MTT normally lasts only for a few months, suggesting a rapid emergence of resistance in the majority of patients. To overcome the resistance to VEGF signaling-targeted MTT, strategies incorporating inhibition of either compensatory pro-angiogenic pathways or recruitment of bone marrow-derived circulating endothelial progenitors, as well as suppression of other oncogenic pathways, are currently being investigated. The combination of multiple molecular targeted agents or the use of multi-target agents may enhance the efficacy at the expense of increased toxicities. To facilitate the development of MTT for HCC, current methodologies for pharmacodynamic assessment, patient selection and target identification need to be improved. Patient selection according to the individual molecular signature of the tumor and correlative biomarker studies are encouraged while planning a clinical trial of novel MTT.

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Authors and Affiliations

  1. National Center of Excellence for Clinical Trial and Research, National Taiwan University Hospital, Taipei, Taiwan

    Ying-Chun Shen, Chiun Hsu & Ann-Lii Cheng

  2. Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan

    Ying-Chun Shen

  3. Department of Oncology, National Taiwan University Hospital, No. 7, Chung-Shan South Rd., 100, Taipei, Taiwan

    Ying-Chun Shen, Chiun Hsu & Ann-Lii Cheng

  4. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

    Chiun Hsu & Ann-Lii Cheng

  5. Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan

    Ann-Lii Cheng

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Shen, YC., Hsu, C. & Cheng, AL. Molecular targeted therapy for advanced hepatocellular carcinoma: current status and future perspectives. J Gastroenterol 45, 794–807 (2010). https://doi.org/10.1007/s00535-010-0270-0

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