Abstract 351: Serum ST6GAL1 is a novel biomarker for predicting efficacy of tyrosine kinase inhibitors in hepatocellular carcinoma by detecting FGF19 expressing tumor

2021 ◽  
Author(s):  
Yuta Myojin ◽  
Takahiro Kodama ◽  
Hayato Hikita ◽  
Ryotaro Sakamori ◽  
Tetsuo Takehara
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors

scholarly journals Multidisciplinary Treatment of Advanced Hepatocellular Carcinoma

2020 ◽  
Vol 14 (1) ◽  
pp. 98-102
Author(s):  
Zhe Yang ◽  
Bulat Abdrakhimov ◽  
Shuo Wang ◽  
Qin-Fen Xie ◽  
Shu-Sen Zheng
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Pulmonary Resection ◽  
Multidisciplinary Treatment ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Stage ◽  
Receive Treatment

Current strategy for treatment of hepatocellular carcinoma (HCC) based on Barcelona-Clinic Liver Cancer (BCLC) criteria dictates that patients with advanced-stage HCC are to only receive treatment with tyrosine kinase inhibitors. However, they prolong overall survival just by slightly more than 6 months. In this article, we present a patient with HCC diagnosed at an advanced stage who received multidisciplinary treatment consisting of transarterial chemoembolization, hepatic resection, pulmonary resection, radiofrequency ablation, tyrosine kinase inhibitors, and radiotherapy, and has survived for more than 2 years since diagnosis and counting.

scholarly journals Efficacy of the immune checkpoint inhibitor nivolumab in the treatment of advanced hepatocellular carcinoma with the exhausted possibilities of therapy with tyrosine kinase inhibitors

2021 ◽  
pp. 84-93
Author(s):  
A. Yu. Goryainova ◽  
A. I. Stukan ◽  
R. A. Murashko ◽  
S. V. Sharov ◽  
O. I. Kirsanova ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Side Effects ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Multiple Drug Resistance ◽  
Response To Therapy ◽  
Advanced Hepatocellular Carcinoma ◽  
Surgical Methods ◽  
A Priority

Hepatocellular carcinoma is one of the most formidable and deadly cancers. The limited possibilities of surgical methods of treatment as well as the formation of multiple drug resistance caused by the biological characteristics of both the liver tissue itself and tumor cells with their microenvironment determine the unsatisfactory indicators of relapse free survival and overall survival of patients. In addition, therapy with tyrosine kinase inhibitors, which has become the “gold” standard, has limited possibilities: a large number of side effects significantly reduce the quality of life and adherence to treatment in patients with hepatocellular cancer. The search for molecular biological targets, as well as new therapeutic agents that block these targets, does not always lead to positive results. Immunotherapy in this sense is a priority, having good tolerance, a low number of side effects, no need for additional testing of the patient’s biological material before starting treatment, high efficiency and a long response time. However, there are many unresolved questions about the duration of therapy, predicting its efficacy, the optimal combination of drugs or the use of monotherapy, the formation of priority subgroups of patients. Understanding the mechanisms of immune evasion, an ability that hepatocellular carcinoma possesses, – is the key to successful use of immunotherapeutic agents alone, in combination with tyrosine kinase inhibitors, antiangiogenic drugs or among themselves. This article provides an overview of data from clinical studies of modern drugs for the treatment of hepatocellular carcinoma and describes the mechanism of liver immunological tolerance as a possible predictive marker of sensitivity to immunotherapy. It seems promising to study the role of cells in the microenvironment of hepatocellular carcinoma for predicting the effectiveness of immunotherapy. The clinical example is used to demonstrate the successful experience of using the immunotherapeutic drug nivolumab in the treatment of hepatocellular carcinoma resistance to tyrosine kinase inhibitors. This is a classic example of duration of response to therapy, lack of reactivation of chronic viral hepatitis and controlled toxicity. All these indicators enable the clinician to consider immunotherapy as a priority option for the treatment of inoperable hepatocellular carcinoma. 

scholarly journals Tyrosine Kinase Inhibitors Stimulate HLA Class I Expression by Augmenting the IFNγ/STAT1 Signaling in Hepatocellular Carcinoma Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Aya Takahashi ◽  
Atsushi Umemura ◽  
Kota Yano ◽  
Shinya Okishio ◽  
Seita Kataoka ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Antigen Processing ◽  
Kinase Inhibitors ◽  
Hla Class I ◽  
Class I ◽  
Cell Phenotype ◽  
Erk Pathway ◽  
Stat1 Signaling

Combination treatment with tyrosine kinase inhibitors (TKIs) and immunotherapies has shown efficacy in the treatment of multiple cancers, but the immunomodulatory effect of TKIs on the tumor cell phenotype remains unknown in hepatocellular carcinoma (HCC). Given that human lymphocyte antigen class I (HLA-I) is essential for tumor antigen presentation and subsequent antitumor immunity, we examined the effects of regorafenib, as well as other TKIs (sorafenib, lenvatinib and cabozantinib) on HLA-I expression in HCC cell lines. Regorafenib increased cell surface HLA-I and β2-microglobulin protein expression in the presence of interferon γ (IFNγ). The expressions of various genes associated with the HLA-I antigen processing pathway and its transcriptional regulators were also upregulated by regorafenib. Furthermore, we found that regorafenib had an activating effect on signal transducers and activators of transcription 1 (STAT1), and that regorafenib-induced HLA-I expression was dependent on the augmented IFNγ/STAT1 signaling pathway. Trametinib, an inhibitor of the extracellular signal-regulated kinase (ERK) kinase MEK, also activated IFNγ/STAT1 signaling and increased HLA-I expression, whereas the phosphatidylinositol 3-kinase (PI3K) inhibitor buparlisib did not. Given that regorafenib directly inhibits Raf/MEK/ERK signaling, the downregulation of the MEK/ERK pathway appears to be one of the mechanisms by which regorafenib promotes STAT1 activation. Sorafenib, lenvatinib, and cabozantinib also showed the same effects as regorafenib, while regorafenib had most potent effects on HLA-I expression, possibly dependent on its stronger inhibitory activity against the MEK/ERK pathway. These results support the clinical combination of TKIs with immunotherapy for the treatment of HCC.

Tyrosine kinase inhibitors for unresectable hepatocellular carcinoma in adults

2021 ◽  
Vol 2021 (11) ◽  
Author(s):  
Winson Cheung ◽  
Yuan Xu ◽  
Shiying Kong ◽  
Roberta Elisa Rossi ◽  
Paolo Baldo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Unresectable Hepatocellular Carcinoma

scholarly journals Is There Still a Place for Tyrosine Kinase Inhibitors for the Treatment of Hepatocellular Carcinoma at the Time of Immunotherapies? A Focus on Lenvatinib

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6310
Author(s):  
Marie Decraecker ◽  
Caroline Toulouse ◽  
Jean-Frédéric Blanc
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Standard Of Care ◽  
Special Focus ◽  
Second Line ◽  
First Line ◽  
First Line Therapy ◽  
Therapeutic Algorithms

The systemic treatment of hepatocellular carcinoma is changing rapidly. Three main classes of treatment are now available. Historically, multi-targeted tyrosine kinase inhibitors (TKIs) (sorafenib and lenvatinib as first-line; regorafenib and cabozantinib as second-line) were the first to show an improvement in overall survival (OS). Anti-vascular endothelial growth factor (anti-VEGF) antibodies can be used in first-line (bevacizumab) or second-line (ramucirumab) combination therapy. More recently, immuno-oncology (IO) has profoundly changed therapeutic algorithms, and the combination of atezolizumab-bevacizumab is now the first-line standard of care. Therefore, the place of TKIs needs to be redefined. The objective of this review was to define the place of TKIs in the therapeutic algorithm at the time of IO treatment in first-line therapy, with a special focus on lenvatinib that exhibits one of the higher anti-tumoral activity among TKI in HCC. We will discuss the place of lenvatinib in first line (especially if there is a contra-indication to IO) but also after failure of atezolizumab and bevacizumab. New opportunities for lenvatinib will also be presented, including the use at an earlier stage of the disease and combination with IOs.

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