Multi-stage differentiation defines melanoma subtypes with differential vulnerability to drug-induced iron-dependent oxidative stress
By J. Tsoi, L. Robert, Kim H. T. Paraiso, C. Galvan, K. Sheu, J. Lay, D. Wong, M. Atefi, R. Shirazi, Xiaoyan Wang and 5 more. Cancer Cell, 2018
818 citations recorded by the source corpus.
Summary Malignant transformation can result in melanoma cells that resemble different stages of their embryonic development. Our gene expression analysis of human melanoma cell lines and patient tumors revealed that melanoma follows a two-dimensional differentiation trajectory that can be sub-classified into four progressive subtypes. This differentiation model is associated with subtype-specific sensitivity to iron dependent oxidative stress and cell death known as ferroptosis. Receptor tyrosine kinase mediated resistance to MAPK targeted therapies and activation of the inflammatory signaling associated with immune therapy involves transitions along this differentiation trajectory, which lead to increased sensitivity to ferroptosis. Therefore, ferroptosis-inducing drugs presents an orthogonal therapeutic approach to target the differentiation plasticity of melanoma cells to increase the efficacy of targeted and immune therapies.
Subfields: Computational Theory and Mathematics, Molecular Biology, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/92fb583bf4daa49269e05d4e0e1856d8dadd2805
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In Pulmonary and Respiratory Medicine
Citations in the corpus
- Exogenous Monounsaturated Fatty Acids Promote a Ferroptosis-Resistant Cell State (2019, neutral): “Recent studies show that a more mesenchymal phenotype, de-differentiation, and acquired resistance to targeted inhibitors, can all promote a ferroptosissensitive cell state (Hangauer et al., 2017; Tsoi et al., 2018; Viswanathan et al., 2017).”
- Ferroptosis: mechanisms and links with diseases (2021, background): “Combinational treatment with ferroptosis inducing drugs with vemurafenib, a BRAF kinase inhibitor, results in a substantial decrease in long-term persisting melanoma cell.(185) Furthermore, ferroptosis may participate in tumor immunity.”
- CD8+ T cells regulate tumor ferroptosis during cancer immunotherapy (2019, background): “Interestingly, a recent study reported a role of IFN γ in promoting human melanoma cell line death induced by erastin in vitro 15 .”