Un enzima chiamato EZH2 decide quali cellule tumorali diventeranno metastasi. Non modifica il DNA direttamente: lo avvolge, silenziando i geni che mantengono l'ordine nella divisione cellulare. Il 5% delle cellule del tumore triplo negativo usa questo meccanismo per viaggiare. La buona notizia? Esistono farmaci che bloccano EZH2 e sono già stati approvati.

https://www.futuroprossimo.it/2025/10/ezh2-trovato-linterruttore-delle-metastasi/

#futuroprossimo #EZH2 #cancro #metastasi

Seung Kim, Frederick Dick et al show that resting #Bcells are uniquely sensitive to #EZH2 #polycomb complex inhibition, which activates expression of repetitive genomic elements and subsequent #innateimmune receptor signaling in a form of viral mimicry

https://www.embopress.org/doi/full/10.15252/embj.2023114462

"These data identify developmental lineage as a key determinant of sensitivity to anti-GD2 based immunotherapies and credential #EZH2 inhibitors for clinical testing in combination with anti-GD2 antibody to enhance outcomes for children with #neuroblastoma".

An article that I had missed, by Mabe et al., linking #mesenchymal #tumour cell state, #GD2 expression, #ST8SIA1 expression, and #immunotherapy #TherapyResistance.

https://www.nature.com/articles/s43018-022-00405-x

Sadly, not open access.

Transition to a mesenchymal state in neuroblastoma confers resistance to anti-GD2 antibody via reduced expression of ST8SIA1 - Nature Cancer

Mabe et al. find that GD2 levels correlate with lineage plasticity in neuroblastoma and identify ST8SIA1 as the key enzyme in GD2 synthesis. EZH2 inhibition in mesenchymal neuroblastoma cells elevates ST8SIA1, synergizing with anti-GD2 antibodies.

Nature
New discoveries about #Polycomb #EZH2 function in #MultipleMyeloma and a therapeutic avenue here:
Dissecting and targeting noncanonical functions of EZH2 in multiple myeloma via an EZH2 degrader. Oncogene (2023). https://doi.org/10.1038/s41388-023-02618-5