Precision medicine for hepatocellular carcinoma: driver mutations and targeted therapy

Ding, Xiaoxiao; Zhu, Qing-Ge; Zhang, Shiming; Guan, Lei; Li, Ting; Zhang, Lei; Wang, Shiyang; Ren, Wanli; Chen, Xuemei; Zhao, Jing; Song, Lin; Liu, Zhizhen; Bai, Yang; He, Bing; Zhang, Huqin

doi:10.18632/oncotarget.18382

Cited by 80 publications

(79 citation statements)

References 122 publications

(153 reference statements)

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“…HCC is characterized by extraordinary inter‐ and intra‐tumor molecular heterogeneity, which is probably responsible for the modest therapeutic response to molecular targeted agents. Future studies should aim at better characterizing and stratifying HCC patients into subgroups, according to their molecular profiles, in order to benefit from treatment with single molecular targeted agents or combinations of them under the heterogeneous conditions of HCC tumors …”

Section: Introductionmentioning

confidence: 99%

Targeting HSP90 with the small molecule inhibitor AUY922 (luminespib) as a treatment strategy against hepatocellular carcinoma

Augello

Emma

Cusimano

et al. 2018

Intl Journal of Cancer

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Hepatocellular carcinoma (HCC) is a highly malignant tumor that responds very poorly to existing therapies, most probably due to its extraordinary inter‐ and intra‐tumor molecular heterogeneity. The modest therapeutic response to molecular targeted agents underlines the need for new therapeutic approaches for HCC. In our study, we took advantage of well‐characterized human HCC cell lines, differing in transcriptomic subtypes, DNA mutation and amplification alterations, reflecting the heterogeneity of primary HCCs, to provide a preclinical evaluation of the specific heat shock protein 90 (HSP90) inhibitor AUY922 (luminespib). Indeed, HSP90 is highly expressed in different tumor types, but its role in hepatocarcinogenesis remains unclear. Here, we analyzed HSP90 expression in primary human HCC tissues and evaluated the antitumor effects of AUY922 in vitro as well as in vivo. HSP90 expression was significantly higher in HCC tissues than in cirrhotic peritumoral liver tissues. AUY922 treatment reduced the cell proliferation and viability of HCC cells in a dose‐dependent manner, but did not do so for normal human primary hepatocytes. AUY922 treatment led to the upregulation of HSP70 and the simultaneous depletion of HSP90 client proteins. In addition, in a cell type‐dependent manner, treatment induced either both caspase‐dependent β‐catenin cleavage and the upregulation of p53, or Mcl‐1 expression, or NUPR1 expression, which contributed to the increased efficacy of, or resistance to, treatment. Finally, in vivo AUY922 inhibited tumor growth in a xenograft model. In conclusion, HSP90 is a promising therapeutic target in HCC, and AUY922 could be a drug candidate for its treatment.

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Section: Introductionmentioning

confidence: 99%

Targeting HSP90 with the small molecule inhibitor AUY922 (luminespib) as a treatment strategy against hepatocellular carcinoma

Augello

Emma

Cusimano

et al. 2018

Intl Journal of Cancer

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“…It is estimated that over 50% of new cases of liver cancer in the world occurred in China each year (2). As the most common type of liver cancer, hepatocellular carcinoma (HCC) has a dismal prognosis because most patients (about two thirds) had lost the opportunity of surgical therapy when HCC was detected at advanced stage (3). Surveillance at regular intervals and early diagnosis of HCC is crucial for improving the patients' survival.…”

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confidence: 99%

Combination of triple biomarkers AFP, AFP-L3, and PIVAKII for early detection of hepatocellular carcinoma in China: Expectation

Gao

Song

2017

DD&T

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Hepatocellular carcinoma (HCC) remains a severe health threat in China. Early tumor detection is crucial for improving the prognosis of patients. Currently, ultrasound plus biomarker alpha fetoprotein (AFP) is recommended by Chinese Liver Cancer Diagnosis and Treatment Guidelines in China. However, most HCC continues to be diagnosed beyond an early stage due to insufficient sensitivity and specificity of current surveillance tools, highlighting the need for more accurate biomarkers to improve early HCC detection. In Japan, ultrasound plus triple biomarkers AFP, Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and prothrombin induced by vitamin K absence II (PIVKA II) has been routinely used for HCC surveillance and achieved increased early HCC detection rate. Very recently, the assay of triple biomarkers AFP, AFP-L3, and PIVKA II using μTASWako i30 immuno-analyzer was brought into China. The prospect of the modality of ultrasound plus triple biomarkers for early HCC detection in China is expected in the future.

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“…The mortality rate associated with PLC is 54% worldwide [4], and accurate diagnosis at an early clinical stage is thought to greatly improve treatment efficacy and patient survival. However, after surgery, the high rates of metastasis and recurrence of PLC (mainly HCC) are the main factors affecting prognosis [19]. Therefore, an in-depth study of OM in HCC is essential.…”

Section: Discussionmentioning

confidence: 99%

Carbohydrate antigen-125, calcium, and hemoglobin as predictive clinical indicator for ocular metastasis in male liver cancer patients

Zhu

et al. 2020

Bioscience Reports

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Background Primary liver cancer (PLC) is a common type of cancer among men worldwide. Little is known regarding the relationship of liver cancer with ocular metastasis (OM). Drinking has been also reported to be related not only to the occurrence of liver cancer but also to the causes of some ocular lesions. Purpose A diagnostic standard for the levels of serum biomarkers associated with OM derived from liver cancer in men is urgently needed. Material and methods We examined the association between OM in liver cancer and its serum biomarkers. A total of 1254 male patients with liver cancer were recruited in this retrospective study between July 2002 and December 2012. We assessed the relationship between drinking preference and OM in male patients with liver cancer, and aimed to identify an independent prognostic factor or establish a quantitative indicator for OM. Results By assessing the potential indicators, carbohydrate antigen-125 (CA-125), calcium, and hemoglobin (Hb) were found to be most valuable in the diagnosis of OM in male patients with liver cancer. Conclusion CA-125, calcium, and Hb are independent risk factors of OM in patients with liver cancer who consume alcohol.

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Precision medicine for hepatocellular carcinoma: driver mutations and targeted therapy

Cited by 80 publications

References 122 publications

Targeting HSP90 with the small molecule inhibitor AUY922 (luminespib) as a treatment strategy against hepatocellular carcinoma

Targeting HSP90 with the small molecule inhibitor AUY922 (luminespib) as a treatment strategy against hepatocellular carcinoma

Combination of triple biomarkers AFP, AFP-L3, and PIVAKII for early detection of hepatocellular carcinoma in China: Expectation

Carbohydrate antigen-125, calcium, and hemoglobin as predictive clinical indicator for ocular metastasis in male liver cancer patients

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