Androgen Receptor Could Be a Potential Therapeutic Target in Patients with Advanced Hepatocellular Carcinoma

Takahashi, Koji; Nakamura, Masato; Nakamoto, Shingo; Wu, Shuang; Haga, Yuki; Sasaki, Reina; Jiang, Xia; Yokosuka, Osamu

doi:10.3390/cancers9050043

Cited by 19 publications

(14 citation statements)

References 43 publications

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“…Additional evidence comes from the fact that individuals with HCC express augmented levels of ARs in their tumor tissue and in the surrounding liver (97). These data support the notion that AR could affect HCC progression and that a combination of sorafenib, (kinase inhibitor drug approved for cancer treatment), together with AR inhibitors, might be a potentially improve treatment for patients with advanced HCC (98).…”

Section: Introductionsupporting

confidence: 80%

Liver and Steroid Hormones—Can a Touch of p53 Make a Difference?

et al. 2019

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The liver is the main metabolic organ in the body, serving as a significant hormonal secretory gland and functioning to maintain hormone balance and homeostasis. Steroid hormones regulate various biological pathways, mainly in the reproductive system and in many metabolic processes. The liver, as well as steroid hormones, contribute significantly, through functional intertwine, to homeostasis maintenance, and proper responses during stress. Malfunction of either has a significant impact on the other and may lead to severe liver diseases as well as to several endocrine syndromes. Thus, the regulation on liver functions as on steroid hormones levels and activities is well-controlled. p53, the well-known tumor suppressor gene, was recently found to regulate metabolism and general homeostasis processes, particularly within the liver. Moreover, p53 was shown to be involved in steroid hormones regulation. In this review, we discuss the bi-directional regulation of the liver and the steroid hormones pointing to p53 as a novel regulator in this axis. A comprehensive understanding of the molecular mechanisms of this axis may help to prevent and treat related disease, especially with the increasing exposure of the population to environmental steroid hormones and steroid hormone-based medication.

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Section: Introductionsupporting

confidence: 80%

Liver and Steroid Hormones—Can a Touch of p53 Make a Difference?

et al. 2019

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“…Irrespective of the etiology, the morbidity of liver cancer in males is 2–4-fold higher compared with that in females (3). A number of studies have suggested that the androgen receptor (AR) may be responsible for the sex disparity observed in liver cancer (76,77). Of note, a study has reported that the transcription and splicing of ANXA7 is regulated by AR-signaling in prostate cancer (78).…”

Section: Discussionmentioning

confidence: 99%

Expression levels and prognostic values of annexins in liver cancer

et al. 2019

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Annexins are a superfamily of calcium-dependent phospholipid-binding proteins that are implicated in a wide range of biological processes. The annexin superfamily comprises 13 members in humans (ANXAs), the majority of which are frequently dysregulated in cancer. However, the expression patterns and prognostic values of ANXAs in liver cancer are currently largely unknown. The present study aimed to analyze the expression levels of ANXAs and survival data in patients with liver cancer from the Oncomine, GEPIA, Kaplan-Meier plotter and cBioPortal for Cancer Genomics databases. The results demonstrated that ANXA1, A2, A3, A4 and A5 were upregulated, whereas ANXA10 was downregulated in liver cancer compared with normal liver tissues. The expression of ANXA10 was associated with pathological stage. High expression levels of ANXA2 and A5 were significantly associated with poor overall survival (OS) rate whereas ANXA7 and A10 were associated with increased OS. The prognostic values of ANXAs in liver cancer were determined based on sex and clinical stage, which revealed that ANXA2, A5, A7 and A10 were associated with OS in male, but not in female patients. In addition, the potential biological functions of ANXAs were identified by Gene Ontology functional annotation and Kyoto Encyclopedia of Genes Genomes pathway analysis; the results demonstrated that ANXAs may serve a role in liver cancer through the neuroactive ligand-receptor interaction pathway. In conclusion, the results of the present study suggested that ANXA1, A2, A3, A4, A5 and A10 may be potential therapeutic targets for liver cancer treatment, and that ANXA2, A5, A7 and A10 may be potential prognostic biomarkers of liver cancer.

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“…HCC is the 4th most common neoplasm and the 2nd commonest cause of cancer deaths in the world. Notably, HCC is a male-dominant disease, with the incidence of HCC ~3-fold higher in males than in females [10]. Hepatitis B virus (HBV) infection is associated with the higher HCC incidence in persons with cirrhosis, occurring in high endemic areas and in Western countries (5-year cumulative incidence, 15% and 10%, respectively) [11].…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanisms Driving Progression of Liver Cirrhosis towards Hepatocellular Carcinoma in Chronic Hepatitis B and C Infections: A Review

Kanda

Goto

Hirotsu

et al. 2019

IJMS

Self Cite

209

145

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Almost all patients with hepatocellular carcinoma (HCC), a major type of primary liver cancer, also have liver cirrhosis, the severity of which hampers effective treatment for HCC despite recent progress in the efficacy of anticancer drugs for advanced stages of HCC. Here, we review recent knowledge concerning the molecular mechanisms of liver cirrhosis and its progression to HCC from genetic and epigenomic points of view. Because ~70% of patients with HCC have hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection, we focused on HBV- and HCV-associated HCC. The literature suggests that genetic and epigenetic factors, such as microRNAs, play a role in liver cirrhosis and its progression to HCC, and that HBV- and HCV-encoded proteins appear to be involved in hepatocarcinogenesis. Further studies are needed to elucidate the mechanisms, including immune checkpoints and molecular targets of kinase inhibitors, associated with liver cirrhosis and its progression to HCC.

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Androgen Receptor Could Be a Potential Therapeutic Target in Patients with Advanced Hepatocellular Carcinoma

Cited by 19 publications

References 43 publications

Liver and Steroid Hormones—Can a Touch of p53 Make a Difference?

Liver and Steroid Hormones—Can a Touch of p53 Make a Difference?

Expression levels and prognostic values of annexins in liver cancer

Molecular Mechanisms Driving Progression of Liver Cirrhosis towards Hepatocellular Carcinoma in Chronic Hepatitis B and C Infections: A Review

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