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miRNA-Based Therapy Development for Pancreatic Cancer
MicroRNAs (miRNA) play an important role in tumorigenesis, cell proliferation, differentiation, invasion, angiogenesis, and metastasis by activating or inhibiting oncogenic molecular pathways across multiple cancer types. Alfa Cytology has a deep understanding of the miRNA role and mechanism in pancreatic cancer, helping our clients to identify new molecular targets and develop new pancreatic cancer-targeted therapies.
Introduction to miRNA in Pancreatic Cancer
As one of the deadliest types of cancer, pancreatic cancer has a survival rate of only about 2% within 5 years of diagnosis. miRNA-based therapy is a powerful tool for cancer prevention and therapy with two main strategies, inhibition of oncogenic miRNA (oncomiRs) and increasing the level of tumor suppressor miRNAs.
Fig 1. microRNAs hold promise as biomarkers, prognostic agents, and advanced pancreatic therapies. (Daoud AZ., et al.; 2019)
miRNAs may function as tumor suppressors or oncomiRs, and their expression is frequently dysregulated in tumors. Tumor suppressor miRNAs typically suppress the expression of oncogenes and genes that promote cell proliferation, migration/invasion, and tumorigenesis. While oncomiRs promote cancer development by negatively regulating tumor suppressor genes. Previous studies have shown that the expression of oncomiRs is increased in cancer cell lines and patient tumors, while the expression of tumor suppressors tends to be reduced, stopped, or lost. Thus, miRNAs are potential targets for therapeutic interventions.
Our Services
The introduction of tumor suppressor miRNAs as well as oncogenic miRNA antagonists may have anti-cancer effects, inhibit pancreatic cancer cell proliferation and invasion, and promote apoptosis, providing a basis for the application of miRNAs in pancreatic cancer therapy. The following are some miRNAs that are overexpressed and down-regulated in pancreatic cancer. We have the capability to design and produce natural and chemically modified RNA.
| Overexpressed miRNA | Down-expressed miRNA |
|---|---|
| miR-10b, miR-21, miR-23a, miR-31, miR-100miR-143, miR-145, miR-146a, miR-150, miR-155, miR-181a/b/c, miR-196a/b, miR-21, miR-210, miR-221, miR-222, miR-223, miR-376a and miR-301 |
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- miRNA Design and Synthesis
We focus on miRNA mimics and inhibitors. During miRNA mimics design and production, we use multiple chemical modifications to improve their stability, binding affinity, protection against nucleases, and pharmacokinetic properties. While miRNA inhibitors are designed to specifically block the upregulated expression of miRNAs associated with cancer development. We can target specific miRNAs and produce related antisense oligonucleotides (ASOs) or antagomir.
- miRNA Modifications
Since RNA molecules are quite unstable due to their 2'-OH chemical group. We offer a series of chemically modifications to stabilize and reduce the high reactivity of RNA molecules, including 2'-O-methyl (2'-OMe), locked nucleic acid (LNA), and phosphorothioate.
- Development of miRNA Delivery System for Pancreatic Cancer Therapy
In addition to stability, another challenge for miRNA-based therapies is the delivery of these RNA drugs to the desired site of action. There is an urgent need to select and design effective vectors for miRNA delivery through the dense fibrous stroma of pancreatic cancer. Through our advanced delivery system platform, we can provide viral vectors, lipid nanoparticles (LNPs) and exosomes to further facilitate the development of miRNA-based drugs for pancreatic cancer.
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Scientific Excellence
Customized Solutions
Collaborative Approach
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For more details on how we advance your innovation miRNA drug development projects, please feel free to contact us. We are ready to assist you.
References
- Chu, Xiangyu, et al. "MicroRNAs as potential therapeutic targets for pancreatic cancer." Chinese Medical Journal 135.01 (2022): 4-10.
- Gurbuz, Nilgun, and Bulent Ozpolat. "MicroRNA-based targeted therapeutics in pancreatic cancer." Anticancer research 39.2 (2019): 529-532.
- Fesler, Andrew, and Jingfang Ju. "Development of microRNA-based therapy for pancreatic cancer." Journal of pancreatology 2.04 (2019): 147-151.
- Daoud AZ, et al. MicroRNAs in Pancreatic Cancer: biomarkers, prognostic, and therapeutic modulators. BMC Cancer. 2019;19(1):1130. Published 2019 Nov 21. doi:10.1186/s12885-019-6284-y
