The fatality rate for uveal melanoma, a rare and dangerous eye disease, has remained unchanged for the past 40 years. New treatments to preserve eyesight and avoid mortality are urgently needed because half of the melanomas spread to other body organs, resulting in death in less than a year.
Researchers have discovered a small chemical inhibitor that dampens the tumor’s powerful drivers in a preclinical investigation. The inhibitor, KCN1, significantly reduced primary disease in the eye and metastatic tumor propagation to the liver in mouse models, and the animals lived longer with no noticeable side effects. The medicine needs some improvement before clinical trials.
Preclinical research suggests that it is possible to develop the KCN1 arylsulfonamide scaffold into a potential treatment for patients with metastatic uveal melanoma. According to the findings, KCN1 has good qualities as a metastasis suppressor: it is well-tolerated, has good distribution in the eye and liver, and is thus well-suited for treating metastatic uveal melanoma.
Previously, little was known of the role of HIF in directing pro-invasive extracellular matrix remodeling in uveal melanoma (UM). HIF regulates tumor cell proliferation, migration, invasion, and adhesion and promotes blood vessel growth to feed the tumor.
Hypoxia promotes collagen deposition, partly because HIF increases the production of two gene products. P4HA1/2 expression correlated with poor overall survival in patients with metastatic UM. The inhibitor KCN1 was most effective at reducing metastases when administered early.
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