Overcoming Treatment Resistance in Hepatocellular Carcinoma: Regorafenib and Lessons from Other Malignancies

2017 ◽  
pp. 133-142
Author(s):  
Bingnan Zhang ◽  
Richard S. Finn
Keyword(s):  
Hepatocellular Carcinoma ◽  
Treatment Resistance

scholarly journals Immunotherapy Updates in Advanced Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2164
Author(s):  
Amisha Singh ◽  
Ryan J. Beechinor ◽  
Jasmine C. Huynh ◽  
Daneng Li ◽  
Farshid Dayyani ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Treatment Options ◽  
Tumor Development ◽  
Treatment Resistance ◽  
Advanced Hepatocellular Carcinoma ◽  
Line Treatment ◽  
Front Line ◽  
T Cell Therapy ◽  
Advanced Hcc ◽  
The Impact

Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide. HCC tumor development and treatment resistance are impacted by changes in the microenvironment of the hepatic immune system. Immunotherapy has the potential to improve response rates by overcoming immune tolerance mechanisms and strengthening anti-tumor activity in the tumor microenvironment. In this review, we characterize the impact of immunotherapy on outcomes of advanced HCC, as well as the active clinical trials evaluating novel combination immunotherapy strategies. In particular, we discuss the efficacy of atezolizumab and bevacizumab as demonstrated in the IMbrave150 study, which created a new standard of care for the front-line treatment of advanced HCC. However, there are multiple ongoing trials that may present additional front-line treatment options depending on their efficacy/toxicity results. Furthermore, the preliminary data on the application of chimeric antigen receptor (CAR-T) cell therapy for treatment of HCC suggests this may be a promising option for the future of advanced HCC treatment.

scholarly journals Identification of Key Functional Modules and Immunomodulatory Regulators of Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Ding Luo ◽  
Xiang Zhang ◽  
Xiao-Kai Li ◽  
Gang Chen
Keyword(s):  
Hepatocellular Carcinoma ◽  
Therapeutic Targets ◽  
Treatment Resistance ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Pathway Enrichment Analysis ◽  
Functional Modules ◽  
Hub Genes ◽  
Gene Set

Despite the advances in the treatment of hepatocellular carcinoma (HCC), the prognosis of HCC patients remains unsatisfactory due to postsurgical recurrence and treatment resistance. Therefore, it is important to reveal the mechanisms underlying HCC and identify potential therapeutic targets against HCC, which could facilitate the development of novel therapies. Based on 12 HCC samples and 12 paired paracancerous normal tissues, we identified differentially expressed mRNAs and lncRNAs using the “limma” package in R software. Moreover, we used the weighted gene coexpression network analysis (WGCNA) to analyze the expression data and screened hub genes. Furthermore, we performed pathway enrichment analysis based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. In addition, the relative abundance of a given gene set was estimated by single-sample Gene Set Enrichment Analysis. We identified 687 differentially expressed mRNAs and 260 differentially expressed lncRNAs. A total of 6 modules were revealed by WGCNA, and MT1M and MT1E genes from the red module were identified as hub genes. Moreover, pathway analysis revealed the top 10 enriched KEGG pathways of upregulated or downregulated genes. Additionally, we also found that CD58 might act as an immune checkpoint gene in HCC via PD1/CTLA4 pathways and regulate the levels of tumor-infiltrating immune cells in HCC tissues, which might be an immunotherapeutic target in HCC. Our research identified key functional modules and immunomodulatory regulators for HCC, which might offer novel diagnostic biomarkers and/or therapeutic targets for cancer immunotherapy.

scholarly journals Self-Amplification of Oxidative Stress with Tumor Microenvironment-Activatable Iron-Doped Nanoplatform for Targeting Hepatocellular Carcinoma Synergistic Cascade Therapy and Diagnosis

2021 ◽  
Author(s):  
Qiao-Mei Zhou ◽  
Yuan-Fei Lu ◽  
Jia-Ping Zhou ◽  
Xiao-Yan Yang ◽  
Xiao-Jie Wang ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Hepatocellular Carcinoma ◽  
Magnetic Resonance ◽  
Tumor Microenvironment ◽  
Rapid Development ◽  
Treatment Resistance ◽  
Resonance Imaging ◽  
Chemotherapy Drugs ◽  
Iron Doped ◽  
Therapy And Diagnosis

Abstract Background The rapid development of hepatocellular carcinoma (HCC) treatment resistance has become a technical bottleneck for clinical treatment. Conventional chemotherapy has long been regarded as ineffective against HCC because of the insensitivity to chemotherapy drugs. Ferroptosis is a form of programmed cell death with a definite Fenton reaction mechanism that converts endogenous hydrogen peroxide (H2O2) into highly toxic hydroxyl radicals (·OH). Therefore, we have developed an ultrasensitive iron-doped magnetic mesoporous silica nanoplatform (DOX@Fe-HMON-Tf NPs) for HCC-targeted synergistic cascade therapy and diagnosis. Results This organic/inorganic nanoplatform consists of a silica shell doped with iron and bis[3-(triethoxysilyl)propyl]tetrasulfide (BTES) and the etched core loaded DOX that generate H2O2 in situ to enhance the ferroptosis effect. DOX@Fe-HMON-Tf NPs can efectively internalized into hepatoma cells by precise delivery through the transferrin grafted with polyethylene glycol (PEG) outside the shell. The resulting nanoplatform can be activated by the tumor microenvironment (TME) in which the glutathione (GSH)-responsive biodegradability could synergize with the therapeutic interaction between DOX and iron and induce tumor cells death through complementary ferroptosis and apoptosis mechanisms. At the same time, the nanoplatform has a superparamagnetic framework that can be used for treatment guidance and monitoring under the guidance of T2-weighted magnetic resonance imaging (MRI). Conclusion The rationally designed nanoplatform provides a new strategy for anti-tumor effects with self-amplified synergistic chemotherapy and chemodynamic therapy (CDT) based on ferroptosis, and magnetic resonance imaging that realizes the integration of diagnosis, treatment and monitoring.

scholarly journals Emerging Regulatory Mechanisms Involved in Liver Cancer Stem Cell Properties in Hepatocellular Carcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Duoduo Lv ◽  
Liyu Chen ◽  
Lingyao Du ◽  
Lingyun Zhou ◽  
Hong Tang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Signaling Pathways ◽  
Primary Liver Cancer ◽  
Treatment Resistance ◽  
Current Evidence ◽  
New Developments ◽  
Regulatory Pathways ◽  
Liver Cancer Stem Cell ◽  
Improve Patient

Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer and one of the leading causes of cancer-related deaths worldwide. A growing body of evidence supports the hypothesis that HCC is driven by a population of cells called liver cancer stem cells (LCSCs). LCSCs have been proposed to contribute to malignant HCC progression, including promoting tumor occurrence and growth, mediating tumor metastasis, and treatment resistance, but the regulatory mechanism of LCSCs in HCC remains unclear. Understanding the signaling pathways responsible for LCSC maintenance and survival may provide opportunities to improve patient outcomes. Here, we review the current literature about the origin of LCSCs and the niche composition, describe the current evidence of signaling pathways that mediate LCSC stemness, then highlight several mechanisms that modulate LCSC properties in HCC progression, and finally, summarize the new developments in therapeutic strategies targeting LCSCs markers and regulatory pathways.

Multimodality treatment of hepatocellular carcinoma

1998 ◽  
Vol 13 (11-s4) ◽  
pp. S315-S319 ◽  
Author(s):  
ZHAO-YOU TANG ◽  
XIN-DA ZHOU ◽  
ZENG-CHEN MA ◽  
ZHI-QUAN WU ◽  
JIA FAN ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Multimodality Treatment

Hepatocellular carcinoma

1982 ◽  
Vol 118 (1) ◽  
pp. 69-70 ◽  
Author(s):  
A. J. Bennett
Keyword(s):  
Hepatocellular Carcinoma
Sign in / Sign up

Export Citation Format

Share Document