Although targeted therapies have been developed for melanoma patients, tumor progression eventually results. Understanding characteristics of melanoma associated with treatment resistance is important for prolonging therapy effectiveness.
In a retrospective study of patients treated with BRAF and/or MEK inhibitors, Chi Yan, PhD, Ann Richmond, PhD, and colleagues discovered an association between tumor progression and an increase in melanoma cells bearing SOX10, a protein required for melanoma tumor growth.
Reporting in the journal npj Precision Oncology, the researchers found a close physical association of SOX10+ melanoma cells with CD8+ T cells correlated with shorter progression-free survival of patients treated with BRAF/MEK inhibitors.
SOX10 had independent and added prognostic value for late- and early-stage melanoma, respectively: patients with high SOX10/low CD8 tumors had a worse overall survival than those with low SOX10/high CD8 tumors.
While further research is needed, targeting the melanoma – T-cell interaction, particularly through exclusion of SOX10+ melanoma cells or reversion of T-cell suppression, potentially could prevent acquired resistance to BRAF/MEK-targeted therapy.
The research was supported in part by a Merit Award and Senior Research Career Scientist Award from the U.S. Department of Veterans Affairs, and National Institutes of Health grant CA116021.
