Methods of prognosis and treatment of patients suffering from melanoma

Abstract

Melanoma cell plasticity plays a key role in the acquisition of resistance to therapy. TRIM24 / TIF1α, which encodes for the tripartite RING / B-Box / Coil-coiled transcriptional coactivator, is frequently amplified in human melanomas. The inventors observed a strong correlation between elevated TRIM24 expression and metastatic disease, adverse outcome to immune checkpoint inhibitor therapy and a worse relapse-free survival. shRNA-mediated knock-down of TRIM24 decreased the migratory capacities and increased the sensitivity to BRAF inhibitors in two cellular melanoma models. RNA-sequencing analyses revealed that TRIM24 knock-down significantly represses undifferentiated / invasive transcriptional programs. A protac-based approach for degradation of Trim24 was shown to resensitize resistant melanoma cells to BRAF inhibitors. Thus, the present invention relates to a method for predicting the survival time of a patient suffering from melanoma comprising the step of measuring the level of TRIM24, and the use of TRIM24 inhibitor for treating melanoma, in particular resistant melanoma.

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