Uveal Melanoma (UM)
Uveal melanoma is a rare eye cancer that begins in the uvea, the middle layer of the eye, which includes the iris, ciliary body, and choroid. This cancer originates from melanocytes, the cells that produce pigment, which can become cancerous within the uvea, resulting in uveal melanoma. Our company is well-equipped to address your drug and therapy development requirements in Uveal Melanoma therapy.
Introduction to Uveal Melanoma
Uveal melanoma is the most common primary intraocular malignancy in adults, constituting about 5% of all melanoma cases. It predominantly affects older individuals, with an annual incidence rate of approximately 2,000 cases in the United States. This cancer primarily involves the choroid (85% of cases), with fewer occurrences in the iris and ciliary body. Despite being rare, uveal melanoma is aggressive, with about 50% of individuals developing metastatic disease, primarily to the liver.
Pathogenesis of Uveal Melanoma
The pathogenesis of uveal melanoma involves a complex interplay of genetic mutations and molecular pathways. Key genetic drivers include mutations in GNAQ, GNA11, BAP1, SF3B1, and EIF1AX, which contribute to tumor initiation and progression. Uveal melanoma cells disseminate hematogenously, showing a unique propensity to metastasize to the liver. This process is influenced by the tumor microenvironment and specific signaling pathways, such as MAPK and PI3K/AKT.
Fig. 1 Growth patterns of metastatic uveal melanoma in the human liver. (Kedarisetti, K.C., et al., 2022)Biomarkers Development of Uveal Melanoma
The identification of biomarkers has enhanced the diagnostic and prognostic capabilities for uveal melanoma. Liquid biopsy techniques, including the analysis of circulating tumor DNA (ctDNA), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs), offer non-invasive methods to monitor tumor dynamics and metastatic potential. Proteomic approaches have identified several potential biomarkers, such as PRAME (preferentially expressed antigen in melanoma), which is an independent predictor of metastasis.
Therapeutics Development of Uveal Melanoma
Small molecule drugs target specific pathways and mutations in uveal melanoma. Two primary pathways are often targeted: the MAPK/ERK and PI3K/AKT pathways. Selumetinib, a MEK inhibitor, showed initial promise in inhibiting tumor growth.
An innovative approach is using genetically modified T cells, such as chimeric antigen receptor (CAR) T cells and T cell receptor (TCR) engineered T cells. These therapies have shown potential, particularly in targeting antigens like PRAME and gp100.
Gene therapy for UM involves altering genetic material to treat or prevent disease. This can include directly targeting mutations like GNAQ and GNA11 or modulating gene expression pathways involved in UM progression. Techniques such as CRISPR/Cas9 are being explored to edit these genes directly.
Monoclonal antibodies (mAbs) are designed to target specific proteins on cancer cells. Immune checkpoint inhibitors (ICIs) like pembrolizumab (anti-PD-1) and ipilimumab (anti-CTLA-4) have been tested in UM. Unfortunately, UM has shown limited response to these therapies compared to cutaneous melanoma.
Our Services
Our company adopts a partnership-driven approach. We collaborate closely with clients to craft tailored, innovative Uveal Melanoma therapy strategies and ensure robust support throughout the process.
Platforms of Uveal Melanoma Therapy Development
Animal Models of Uveal Melanoma
We have established expertise in developing and utilizing relevant animal models that closely mimic the disease characteristics and response to therapy. These models enable us to evaluate the safety and efficacy of potential therapies.
| Non-Genetically Engineering Models | ||
| We provide diverse model choices customized to meet specific research needs related to Uveal Melanoma. These models allow researchers to simulate and study the complex biological processes associated with Uveal Melanoma. | ||
| Optional Models |
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| Genetically Engineered Models | ||
| Our expertise in genetic engineering techniques, such as CRISPR/Cas9 technology, allows us to generate accurate and reliable models that recapitulate the genetic alterations observed in human Uveal Melanoma. | ||
| Optional Models |
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| Optional Species | Mice, Rats, Non-human primates, Others | |
In addition to these models, our comprehensive services encompass other models that target specific signaling pathways and molecular targets.
If our services align with your goals, please contact us for more details.
References
- Rantala, E.S., et al., "Metastatic uveal melanoma: The final frontier." Prog Retin Eye Res, (2022). 90: p. 101041.
- Chattopadhyay, C., et al., "Uveal melanoma: From diagnosis to treatment and the science in between." Cancer, (2016). 122(15): p. 2299-2312.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.