Extended Data Fig. 6: Inhibition of ALK-mediated phosphorylation of CDK9 at Y19 results in accumulation of DNA damage after treatment with PARPi in PARPi-resistant cells. | Nature Cancer

Extended Data Fig. 6: Inhibition of ALK-mediated phosphorylation of CDK9 at Y19 results in accumulation of DNA damage after treatment with PARPi in PARPi-resistant cells.

From: Targeting the ALK–CDK9-Tyr19 kinase cascade sensitizes ovarian and breast tumors to PARP inhibition via destabilization of the P-TEFb complex

Extended Data Fig. 6

Representative images of DAPI, γH2AX, and EdU staining in PARPi-resistant SKOV3 cells depleted of endogenous CDK9 and re-constituted with PCDH (vector control), WT, Y19E, or Y19F CDK9. These cells were cultured with 0.25 μM PARPi (talazoparib) or 0.5 μM ALKi (lorlatinib), either alone or in combination, for 48 hours. Insets, 3.3× magnification. Bar, 20 µm. Data are representative of N = 3 independent experiments with similar results.

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