scholarly journals Updates in the Systemic Treatment of Hepatocellular Carcinoma

2018 ◽  
Vol 14 (2) ◽  
pp. 76
Author(s):  
Emerson Y Chen ◽  
Charles D Lopez ◽  
Gina M Vaccaro ◽  
◽  
◽  
...  

Oncology drug development has recently introduced new systemic treatment options for hepatocellular carcinoma (HCC). Here we consider the general approaches to diagnostic workup, staging, and overall management of HCC with emphasis on systemic treatment options based on recent phase III clinical trials. Novel drug targets involving immunotherapy may change how we treat HCC in the near future.

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Christos Dimitrakopoulos ◽  
Sravanth Kumar Hindupur ◽  
Marco Colombi ◽  
Dritan Liko ◽  
Charlotte K. Y. Ng ◽  
...  

Abstract Background Genetic aberrations in hepatocellular carcinoma (HCC) are well known, but the functional consequences of such aberrations remain poorly understood. Results Here, we explored the effect of defined genetic changes on the transcriptome, proteome and phosphoproteome in twelve tumors from an mTOR-driven hepatocellular carcinoma mouse model. Using Network-based Integration of multi-omiCS data (NetICS), we detected 74 ‘mediators’ that relay via molecular interactions the effects of genetic and miRNA expression changes. The detected mediators account for the effects of oncogenic mTOR signaling on the transcriptome, proteome and phosphoproteome. We confirmed the dysregulation of the mediators YAP1, GRB2, SIRT1, HDAC4 and LIS1 in human HCC. Conclusions This study suggests that targeting pathways such as YAP1 or GRB2 signaling and pathways regulating global histone acetylation could be beneficial in treating HCC with hyperactive mTOR signaling.


BMJ ◽  
2020 ◽  
pp. m3544 ◽  
Author(s):  
Ju Dong Yang ◽  
Julie K Heimbach

ABSTRACT Hepatocellular carcinoma is one of the leading causes of cancer related death in the world. Biannual surveillance for the disease in patients with cirrhosis and in high risk carriers of hepatitis B virus allows early stage cancer detection and treatment with good long term outcomes. Liver ultrasonography and serum α fetoprotein are the most commonly used surveillance tests. If suspicious results are found on the surveillance test, multiphasic computed tomography or magnetic resonance imaging should be undertaken to confirm the diagnosis of hepatocellular carcinoma. If radiologic tests show inconclusive results, liver biopsy or repeat imaging could be considered for confirmation of hepatocellular carcinoma. Management of the disease is complex. Patients should be evaluated by a multidisciplinary team, and the selection of treatment should consider factors such as tumor burden, severity of liver dysfunction, medical comorbidities, local expertise, and preference of patients. Early stage hepatocellular carcinoma is best managed by curative treatment, which includes resection, ablation, or transplantation. Patients with intermediate stage disease often receive locoregional treatment. Systemic treatment is reserved for patients with advanced disease. Several positive, phase III, randomized controlled trials have expanded the systemic treatment options for advanced hepatocellular carcinoma with promising long term outcomes, especially trials using combination treatments, which could also have eventual implications for the treatment of earlier stage disease.


Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2540
Author(s):  
Constanze Mittermeier ◽  
Andreas Konopa ◽  
Susanne Muehlich

Hepatocellular carcinoma (HCC) has emerged as a major cause of cancer-related death and is the most common type of liver cancer. Due to the current paucity of drugs for HCC therapy there is a pressing need to develop new therapeutic concepts. In recent years, the role of Serum Response Factor (SRF) and its coactivators, Myocardin-Related Transcription Factors A and B (MRTF-A and -B), in HCC formation and progression has received considerable attention. Targeting MRTFs results in HCC growth arrest provoked by oncogene-induced senescence. The induction of senescence acts as a tumor-suppressive mechanism and therefore gains consideration for pharmacological interventions in cancer therapy. In this article, we describe the key features and the functional role of senescence in light of the development of novel drug targets for HCC therapy with a focus on MRTFs.


2020 ◽  
Vol 19 (5) ◽  
pp. 300-300 ◽  
Author(s):  
Sorin Avram ◽  
Liliana Halip ◽  
Ramona Curpan ◽  
Tudor I. Oprea

2021 ◽  
Vol 9 (4) ◽  
pp. 826
Author(s):  
Dorien Mabille ◽  
Camila Cardoso Santos ◽  
Rik Hendrickx ◽  
Mathieu Claes ◽  
Peter Takac ◽  
...  

Human African trypanosomiasis is a neglected parasitic disease for which the current treatment options are quite limited. Trypanosomes are not able to synthesize purines de novo and thus solely depend on purine salvage from the host environment. This characteristic makes players of the purine salvage pathway putative drug targets. The activity of known nucleoside analogues such as tubercidin and cordycepin led to the development of a series of C7-substituted nucleoside analogues. Here, we use RNA interference (RNAi) libraries to gain insight into the mode-of-action of these novel nucleoside analogues. Whole-genome RNAi screening revealed the involvement of adenosine kinase and 4E interacting protein into the mode-of-action of certain antitrypanosomal nucleoside analogues. Using RNAi lines and gene-deficient parasites, 4E interacting protein was found to be essential for parasite growth and infectivity in the vertebrate host. The essential nature of this gene product and involvement in the activity of certain nucleoside analogues indicates that it represents a potential novel drug target.


2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Marie O. Pohl ◽  
Jessica von Recum-Knepper ◽  
Ariel Rodriguez-Frandsen ◽  
Caroline Lanz ◽  
Emilio Yángüez ◽  
...  

Author(s):  
Eamonn Morrison ◽  
Patty Wai ◽  
Andri Leonidou ◽  
Philip Bland ◽  
Saira Khalique ◽  
...  

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