Integrative multi-omics defines melanoma drug response and ARID1A-dependent resistance mechanisms

ABSTRACT: Resistance to BRAF/MAPK inhibitors is a significant challenge in melanoma treatment, driven by adaptive and acquired mechanisms allowing tumour cells to evade therapy. We explored early signalling responses to BRAF and MAPK inhibition in a BRAFV600E-sensitive melanoma cell line and a drug-resistant ARID1A-knockout (KO) derivative. ARID1A, frequently mutated in melanoma, is linked to resistance and immune evasion. Through an innovative systems biology approach integrating multi-omics datasets, we identified critical resistance mechanisms. We found that ARID1A-KO cells exhibited transcriptional rewiring, sustaining MAPK1/3 and JNK activity post-treatment, suppressing PRKD1 activation, increasing JUN activity, and disrupting PKC dynamics via elevated RTKs (e.g., EGFR, ROS1) and Ephrin recepto

SUBMITTER: Charlie, George Barker 

PROVIDER: S-SCDT-10_1038-S44320-025-00183-5 | biostudies-other |

REPOSITORIES: biostudies-other