Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial

Cheng, Ann Lii; Kang, Yoon Koo; Chen, Zhendong; Tsao, Chao Jung; Qin, Shukui; Kim, Jun Suk; Luo, Rong; Feng, Jifeng; Ye, Sheng‐Long; Yang, Tsung‐Ming; Xu, Jianming; Sun, Yan; Liang, Houjie; Liu, Jiwei; Wang, Jiejun; Tak, Won Young; Pan, Hongming; Burock, K.; Zou, J.; Voliotis, D.; Guan, Zhi‐Zhong

doi:10.1016/s1470-2045(08)70285-7

Cited by 5,290 publications

(5,255 citation statements)

References 36 publications

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“…The median OS of HCC is 4 months, and the 5‐year OS is 3%. Although many molecules have been proposed as potential targets for anticancer therapy, so far only sorafenib has been shown to improve median survival in advanced HCC patients (Cheng et al ., 2009; Llovet et al ., 2008). In our study, we found that HDGF expression was higher in cancer tissues than in adjacent noncancerous tissues.…”

Section: Discussionmentioning

confidence: 99%

Role of hepatoma‐derived growth factor in promoting de novo lipogenesis and tumorigenesis in hepatocellular carcinoma

et al. 2018

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Although identified as a growth factor, the mechanism by which hepatoma‐derived growth factor (HDGF) promotes cancer development remains unclear. We found that nuclear but not cytoplasmic HDGF is closely associated with prognosis of hepatocellular carcinoma (HCC). RNA‐sequencing analysis further demonstrated that the nuclear role of HDGF involved regulation of transcription of lipid metabolism genes. HDGF‐induced expression of lipogenic genes was mainly associated with activation of sterol regulatory element binding protein (SREBP) transcription factor. Coexpression of SREBP‐1 and nuclear HDGF predicts poor prognosis for HCC. In addition, by changing the first amino acid of the PWWP domain from proline to alanine, the type of PWWP domain changed from P‐ to A‐type, resulting in inability to induce SREBP‐1‐mediated gene transcription. The type of PWWP domain affects the recruitment of the C‐terminal binding protein‐1 transcriptional repressor on the promoter of the lipogenic gene. Our data indicate that HDGF acts as a coactivator of SREBP1‐mediated transcription of lipogenic genes. The PWWP domain is crucial for HDGF to promote lipogenesis. Moreover, transcriptional regulation of nuclear HDGF plays important roles in the development of HCC.

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Section: Discussionmentioning

confidence: 99%

Role of hepatoma‐derived growth factor in promoting de novo lipogenesis and tumorigenesis in hepatocellular carcinoma

et al. 2018

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“…There was an increase in median time to disease progression (TTP, 2.8 months) in the sorafenib treatment group in comparison to the placebo group (TTP, 1.4 months) [25]. The clinical findings in the SHARP and Asian-Pacific studies indicate the potential therapeutic benefits of single-agent sorafenib in treating advanced HCC.…”

Section: Clinical Trials With Targeted Agents In Hcc (Table 1)mentioning

confidence: 99%

Can we develop effective combination antiangiogenic therapy for patients with hepatocellular carcinoma?

et al. 2011

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Antiangiogenic therapy has shown promise in the treatment of patients with hepatocellular carcinoma (HCC). Bevacizumab, sorafenib, and sunitinib showed efficacy in patients with HCC; and sorafenib is approved by the FDA for treatment of this cancer. In practice, the clinical benefit of these agents has been heterogeneous; and in patients who do respond, the benefit is modest and/or short-lived. Recent advances in the molecular understanding of tumor angiogenesis along with the rapid development of targeted drug discovery have made it possible to explore novel combination therapy for HCC. We review the clinical trial results, discuss possible molecular mechanisms of resistance, and suggest novel combinations with antiangiogenic therapy.

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“…These stages defined the BCLC staging system in the initial proposal, 6 which was prospectively validated by a number of later studies. [22][23][24][25] In addition to these prospective validations, several studies have demonstrated the ability of the model. 26,27 It has been recently endorsed by numerous groups 1,21,28 and is included in the guidelines for the management of HCC from the American Association for the Study of Liver Diseases.…”

Section: Formentioning

confidence: 99%

What is the best staging system for hepatocellular carcinoma in the setting of liver transplantation?

et al. 2011

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Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial

Cited by 5,290 publications

References 36 publications

Role of hepatoma‐derived growth factor in promoting de novo lipogenesis and tumorigenesis in hepatocellular carcinoma

Role of hepatoma‐derived growth factor in promoting de novo lipogenesis and tumorigenesis in hepatocellular carcinoma

Can we develop effective combination antiangiogenic therapy for patients with hepatocellular carcinoma?

What is the best staging system for hepatocellular carcinoma in the setting of liver transplantation?

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