Colorectal Cancer (CRC)
Colorectal Cancer (CRC) typically emerges in the colon or the rectum, and is associated with an abnormal increase in cell division which forms a tumor with the potential to invade other tissues and spread. Protheragen's MyD88-targeted therapy development aims to disrupt TLR/IL-1R-MyD88 crosstalk in the tumor microenvironment (TME), restoring anti-tumor immunity and overcoming chemoresistance.
Overview of Colorectal Cancer
CRC is among the most common causes of cancer death and disability around the world. Its progression follows a multi-step pathway usually accentuated by some alteration within genes and changes in the environment. Precancerous condition chronic inflammation such as that seen in Inflammatory Bowel disease, plays a fundamental role in the disease. Some recent studies suggest that MyD88 signaling could be critically important for inflammation induced CRC tumor development and for the tumor microenvironment.
Pathogenesis of Colorectal Cancer
The pathogenesis of CRC is multifactorial, where inflammation is a major contributing factor. The MyD88-dependent TLR/IL-1R signaling pathways are turned on in the gut and tumor microenvironment in the intestinal epithelial cells and immune cells. Damaged tissues or tumor cells release PAMPs and DAMPs which stimulate these receptors. There is robust activation of the NF-κB/MAPK pathways resulting in the overproduction of proinflammatory cytokines and chemokines, immune recruitment, epithelial cell proliferation alongside growth and survival signaling, genetic instability, and tumor promotion. MyD88 signaling within the tumor microenvironment can drive pro-tumor inflammation and some elements of immunosuppression.
Fig.1 Metformin alleviates colitis-associated colorectal cancer via inhibition of the TLR4/MyD88/NF-κB/MAPK pathway. (Lai et al., 2025)MyD88-Targeted Therapeutic Development for Colorectal Cancer
| Therapy | Mechanism | Key Findings | Stage of Development |
| MyD88 Gene Silencing (siRNA) | Inhibits MyD88-NF-κB/AP-1 signaling pathway, suppressing tumor cell proliferation, migration, and invasion. | In vitro: Significantly reduced proliferation, migration, and invasion of SW480/HCT116 cells. In vivo: Suppressed tumor growth in a HCT116 xenograft nude mouse model. |
Preclinical |
| MyD88 Inhibitor (TJ-M2010-5) | Blocks MyD88 signaling, reducing myeloid-derived suppressor cell (MDSC) generation, expansion, and immunosuppressive functions. | Decreased CD11b+Gr1+ MDSC accumulation and immunosuppressive molecules (iNOS, Arg-1, IDO). Reduced MDSC-mediated suppression of CD4+ T cell proliferation. |
Preclinical |
| MyD88 Inhibitor (TJ-M2010-5) | Maintains gut microbiota homeostasis: Upregulates MUC2 production, enriches probiotics | Restored microbiota balance (dominance of Firmicutes/Bacteroidota). Fecal microbiota transplantation (FMT) from inhibitor-treated mice attenuated CAC progression. |
Preclinical |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen offers specialized services for MyD88-targeted therapeutic discovery and advanced disease models for colorectal cancer. Our integrated platform leverages gut-specific in vitro and in vivo models to enable high-throughput screening and functional evaluation of MyD88 signaling modulators, focusing on chronic inflammation-driven tumorigenesis and chemotherapy resistance in colorectal cancer.
Therapeutic Discovery Platform for Colorectal Cancer
Protheragen's MyD88 discovery platform targets dysregulated immune-metabolic crosstalk between intestinal epithelial cells, tumor-associated macrophages (TAMs), and gut microbiota. The platform accelerates preclinical validation of therapies that disrupt MyD88-dependent pro-tumorigenic networks:
Disease Models Development for Colorectal Cancer
Protheragen provides comprehensive preclinical modeling services for colorectal cancer, including cell-based models, organoid models, and animal models that replicate inflammation-driven tumorigenesis, tumor growth, metastasis, and the tumor microenvironment, enabling mechanistic studies and therapeutic validation.
- TAMs-Organoid Co-Cultures
- Gut-on-a-Chip
- 3D Liver Metastasis Organoids
- Microbiota-Epithelium Interaction Systems
- AOM/DSS-Induced Colorectal Cancer
- Patient-Derived Xenograft (PDX)
- APCmin/+ Spontaneous Models
- hIL-17-Humanized Mice
Protheragen rigorously advances MyD88-targeted therapies for colorectal cancer through a translational framework integrating disease model development, pharmacokinetics and drug safety evaluation, and investigator-initiated trials. Our end-to-end approach bridges preclinical inflammatory and tumor microenvironment insights to early clinical validation, accelerating therapeutic development for CRC treatment and improved outcomes.
If you are interested in our services, please don't hesitate to contact us.
References
- Lai, X., et al. "Metformin Alleviates Colitis-Associated Colorectal Cancer Via Inhibition of the Tlr4/Myd88/Nfkappab/Mapk Pathway and Macrophage M2 Polarization." Int Immunopharmacol 144 (2025): 113683.
- Xie, B., et al. "Blocking Myd88 Signaling with Myd88 Inhibitor Prevents Colitis-Associated Colorectal Cancer Development by Maintaining Colonic Microbiota Homeostasis." Sci Rep 13.1 (2023): 22552.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.