Current research suggests that therapy-induced senescence (TIS) represents a novel functional target that may improve cancer therapy. TIS can be induced in immortal and transformed cancer cells by selected anticancer compounds or radiation, and accumulating data indicate that TIS may produce reduced toxicity-related side effects and increased tumor-specific immune activity.
Oncosence screening platform
A genetic screen for induction of senescence in cancer cells. A). A375-Mir146a-GFP cells were treated with doxorubicin to induce DNA damage, paraquat to induce ROS or EGFR expression to induce oncogenic stress and analyzed for GFP expression and stained for SA- β-gal (lower). B) A375-Mir146a-GFP cells were infected with a CRISPR library targeting 600 epigenetic modifier enzymes. After 8 days, cells were FACS sorted and GFP positive cells isolated. Bar codes were sequenced. C). MA-plot of bar codes in GFP-positive cells. 4 gRNAs for SMARCB1 were enriched. D). gRNAs for SMARCB1 induce GFP-positivity, induce SA-β-gal and induce a senescence morphology.
