Figure 1. RNA-binding proteins as novel oncological targets. (A) Unbiased screen on cell lines with increasing cancer aggressiveness​. (B) Specific inhibition of the RNA binding domain of one of the hit candidate RBPs affects tumoral cells viability.

Novel antitumoral RNA-binding protein targets in melanoma identified by an unbiased screen.

We are finalizing target validation and developing high throughput small molecule screening assays to develop novel compounds that can be used to treat metastatic melanoma.

Technology:

Although immune checkpoint inhibitors and BRAF/MEK targeted therapy, are currently the gold standard in treating melanoma, >50% of melanoma patients will eventually develop resistance. RNA-binding proteins (RBPs), which regulate mRNA fate and function, modulate virtually all cancer hallmarks, and underlie non-genomic mechanisms of cell stress resistance and cancer aggressiveness. Through a novel, unbiased screen, we identified and validated novel RBPs involved in melanoma metastasis, that represent novel and highly potential targets for developing new therapies.

Currently, the team is performing the finalization of target validation and identification of RNA-binders is ongoing. Their aim is to have a screening assay developed and to start hit generation for melanoma during 2024-2025.

Advantages:

• The current known most frequent driver mutations are already present in benign nevi and are not indicative of metastatic outcome.​ Therapeutic solutions targeting genetic drivers are limited to subpopulation of patients.​ Targeting dysregulated post-transcriptional regulation through RBPs that are more prevalent than any eventual driver mutation, will provide a broader range of patients benefiting from the therapy.​
• It will also provide alternatives for patients that develop resistance to current standard therapy.​

References:

Mestre-Farràs et al., Nucleic Acids Research, 2022, Vol. 50, No. 14, 8207-8225..