Dr. Erwin Van Meir and colleagues published a study identifying HIF-regulated genes (P4HA1 and P4HA2) that contribute to the invasion of uveal melanoma cells into surrounding tissues. Importantly, this process could be blocked using a HIF inhibitor, KCN1, that works by the same mechanism of action as 64B, OncoSpherix’s clinical lead HIF inhibitor. The inhibition of HIF by KCN1 or by 64B reduces the growth of uveal melanoma in the eye as well as metastasis to the liver in preclinical mouse models. These reductions in tumor growth and spread are accompanied by improved survival. The new study also found that the genes involved in invasion (P4HA1 and P4HA2) were significantly overexpressed in the primary tumors of patients who developed metastatic disease compared to those who didn’t, suggesting that the presence of high levels of P4HA1 and 2 in eye melanomas can be used to identify patients at high risk for metastasis who might benefit from clinical interventions designed to reduce that risk.
The new article was published in Oncogene 40 (2021) pages 5182-5191. PMID: 34218269
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