Certain cancer drugs inhibit the powerful gene regulator NF-κB, overactivity of which drives some cancers. However, two groups now show that NF-κB also stimulates some tumour cells to senesce, or stop dividing, during chemotherapy. This suggests that, in some patients, NF-κB inhibitors could stimulate rather than inhibit cancer.
Scott Lowe of the Memorial Sloan-Kettering Cancer Center in New York and his colleagues found that NF-κB activates many senescence-associated genes. In a mouse model of lymphoma, inhibiting NF-κB boosted drug resistance and early relapse, and reduced survival.
Clemens Schmitt at the Charité University Hospital in Berlin and his colleagues found that maintaining a senescent cell state using a chemotherapeutic agent requires active NF-κB signalling. Furthermore, the group analysed data from patients with lymphoma and identified a subpopulation in which hyperactive NF-κB signalling is associated with longer survival.