Hepatocellular Carcinoma (HCC)

Hepatocellular Carcinoma (HCC) accounts for nearly 80% of primary liver cancer cases and is often diagnosed during chronic liver disease or cirrhosis. Protheragen offers comprehensive services to devise MyD88-directed therapies for hepatocellular carcinoma and seeks to ameliorate the inflammatory microenvironment that fuels tumor growth.

Introduction to Hepatocellular Carcinoma

HCC is associated with a number of chronic liver infections, including metabolic dysfunction-associated fatty liver disease, alcoholic liver disease, and cirrhosis, making it among the leading causes of cancer death worldwide. The chronic inflammation coupled with oxidative stress from these conditions induces a tumor microenvironment. Newly published studies indicate the MyD88-dependent pathway plays an important role in chronic inflammation as well as in transforming, tumor growth, and immunomodulating liver parenchyma.

Pathogenesis of Hepatocellular Carcinoma

Chronic hepatic inflammation and injury are causative factors to the pathogenesis of HCC. A relentless barrage of causative factors results in hepatocellular injury and damage, leading to activation of liver resident cells, and setting into motion an inflammatory cascade. Release of DAMPs from dead hepatocytes along with PAMPs due to gut dysbiosis leads to the activation of PRRs like TLRs and IL-1Rs expressed on Kupffer cells, HSCs, LSECs, and hepatocytes. This triggers the MyD88 dependent pathway.

Fig.1 An overview of different HCC etiologies and the potential mechanism causing HCC. (Chidambaranathan-Reghupaty, Fisher and Sarkar, 2019)

MyD88-Targeted Therapeutic Development for Hepatocellular Carcinoma

Direct MyD88 Signaling Inhibition

Direct MyD88 Signaling Inhibition Small molecule antagonists like TJ-M2010-5 MyD88 dimerization which blocks the downstream ERK1/2/RSK/GSK3β signaling cascade leading to cell cycle arrest and tumor proliferation reduction. Preclinical studies indicate that it is effective in HCC growth inhibition

Targeting MyD88 Regulatory Networks

Targeting MyD88 Regulatory Networks Novel research has discovered what drives MyD88 overexpression in HCC is the upstream epigenetic regulator, such as the lncRNA Lnc-Myd88, which promotes H3K27 acetylation at MyD88's promoter enhancing NF-kB and PI3K/AKT pathways. The CRISPR-Cas9 silencing of Lnc-Myd88 destroys the MyD88 - mediated tumor progression and metastasis supremacy.

Our Services

Protheragen develops advanced disease models such as and hepatocellular carcinoma MyD88-targeted therapeutic discovery. For screening and evaluation of MyD88 signaling modulators, we employ sophisticated in vitro and in vivo liver-specific systems for TLR/IL-1R driven chronic liver inflammation, fibrogenesis, and HCC development/progression.

Therapeutic Discovery Platform for Hepatocellular Carcinoma

Protheragen's MyD88 platform for hepatocellular carcinoma employs pathway specific modulators with liver inflammation, fibrosis and tumor models to capture the critical effect of innate immunity and inflammation on the HCC pathogenesis. The platform achieves preclinical validation of therapies that seek to disrupt MyD88 dependent pro-tumor inflammatory networks and possibly directly inhibit HCC cell survival and proliferation.

Disease Models Development for Hepatocellular Carcinoma

Protheragen offers full-spectrum preclinical models of hepatocellular carcinoma and related chronic liver disease, spanning cell-based models, organoid models, and animal models that recapitulate the complexity of liver inflammation, fibrogenesis, tumor development, and the tumor microenvironment.

Cell-based & Organoid models

• Immortalized HCC Cell Lines
• Primary HCC Cells
• HCC Organoids
• 3D Bioprinted Models
• Spheroid Co-Cultures

Animal Models Development

• Diethylnitrosamine (DEN)-Induced HCC
• STZ/HFD-Induced NASH-HCC
• Cell Line-Derived Xenografts
• Transgenic MyD88L265P Mice
• Humanized Liver Models

At Protheragen, our therapeutic strategy for MyD88-driven diseases integrates disease model development, pharmacokinetics and drug safety evaluation, and investigator-initiated trials within a unified framework. By combining robust preclinical models with rigorous safety profiling and collaborative early-stage clinical studies, we accelerate the validation of MyD88-targeted therapies.

If you are interested in our services, please don't hesitate to contact us.

References

• Chidambaranathan-Reghupaty, S., P. B. Fisher, and D. Sarkar. "Hepatocellular Carcinoma (Hcc): Epidemiology, Etiology and Molecular Classification." Adv Cancer Res 149 (2021): 1-61.
• Liu, J., et al. "Implication of Myeloid Differentiation Factor 88 Inhibitor Tj-M2010-5 for Therapeutic Intervention of Hepatocellular Carcinoma." Hepatol Res 49.10 (2019): 1182-94.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.