Novel approaches for targeted therapy in CTCL

Abstract

Development of targeted therapy for Cutaneous T-Cell Lymphoma (CTCL) patients still requires actionable mutated genes and deregulated pathways to be identified. Although it has been proposed that neoplastic CTCL cells feature increased TCR downstream signaling and also shows a degree of phenotypic plasticity, the mechanistic nature of the pathogenesis of this disease remains essentially unveiled. Our laboratory has recently studied the mutational status of a number of human CTCL lesions, and detected TCR/PLCG1 and JAK/STAT signaling pathways frequently mutated. Taking advantage of these findings, we have explored the biological effects that targeted inhibition, using specific inhibitors of the two aforementioned signaling pathways, exerts in proliferation, survival and phenotype in a panel of human CTCL cell lines. Our results suggest that TCR/PLCG1 and JAK/STAT pathways can control proliferation, survival and phenotype of CTCL cells and hence can serve as potential targets for mono or combinatorial therapy in CTCL patients.