Céline PISIBON

Research team

Biology and pathologies of melanocytes: From skin pigmentation to melanoma

Investigating the role of CtBP1/2 in melanoma resistance to targeted therapies and immunotherapies

Abstract :

Despite progress in metastatic cutaneous melanoma treatments with targeted therapies and immunotherapies, more than half of patients experience only short-term or no benefit of these therapies due to innate or acquired resistances. It is therefore necessary to find new therapeutic approaches to prevent or overcome these resistances whose causes are often non-genetic and rely on epigenetic reprogramming. These epigenetic alterations can be explained by chromatin remodeling complexes regulation addressed to precise locations in the genome, facilitated by specific interactions with transcription factors binding with their target sequences. In this work, we investigated the role of transcriptional corepressors CtBP1 and CtBP2 in melanoma cells resistance to targeted therapies. Genetic or pharmacological inhibition of CtBP1/2 leads to re-sensitization of resistant melanoma cells to targeted therapies. This re-sensitization is associated with metabolic pathways modulation that could be targeted to improve melanoma treatment. Moreover, we have identified partners of CtBP1/2 and their inhibition resensitizes melanoma cells to targeted therapies. Taken together, our results demonstrate the importance of CtBP1/2 in the resistance of melanoma cells to targeted therapies. Targeting these proteins could be an interesting therapeutic strategy for overcoming resistance to therapies in metastatic melanoma.

Keywords : 

Cutaneous melanoma; epigenetic; drug resistance