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Targeting the eIF4F, Translation Initiation Complex, in Melanoma

Ze'ev Ronai, PhD

Award Type Established Investigator Award
Institution Sanford Burnham Prebys Medical Discovery Institute
The translation initiation complex (or TIC) is one of the last unexplored targets in cancer therapy or melanoma. Protein production is tightly controlled by a complex of four main proteins, which are overexpressed in cancer (including melanoma). As a result, tumor-causing genes are produced more abundantly, promoting cancer and melanoma. Over the past decade, we have been able to characterize small molecule inhibitors that interact with components of this machinery, interfere with its assembly, and yet – cause minimal effects on melanocytes or non-transformed cells, while killing melanoma cells more effectively than other tumors. We propose to select the most effective small molecule inhibitors of this machinery to enable an understanding of how they work and to demonstrate their effectiveness in preclinical models.