Fig. 2. ALK inhibition reduces HR-repair activity in response to DNA damage.
a, Representative images of RAD51 with EdU/DAPI staining in PARP inhibitor-resistant ovarian and TNBC cells treated with 0.25 μM PARP inhibitor (PARPi; talazoparib) or 0.5 μM ALK inhibitor (ALKi; lorlatinib), either alone or in combination, for 48 h. Insets: ×3.3 magnification. Scale bar, 20 µm. Data represent n = 3 independent experiments with similar results. b,c, Quantification of EdU-positive cells with RAD51 (b) and γH2AX (c) foci in PARP inhibitor-resistant ovarian and TNBC cells treated with 0.25 μM PARP inhibitor (talazoparib) or 0.5 μM ALK inhibitor (lorlatinib), either alone or in combination, for 48 h. Error bars represent mean ± s.d. of n = 3 independent experiments. Statistical analysis was carried out using the two-tailed, unpaired Student’s t-test b, Control (Con,○) versus ALK inhibitor (ALKi, ●): *P = 0.0141 in OVCA433, **P = 0.0014 in SKOV3, **P = 0.0038 in TNBC-R no. 6, *P = 0.0122 in TNBC-R no. 15; PARP inhibitor (PARPi, □) versus PARP inhibitor + ALK inhibitor (PARPi + ALKi, ■): **P = 0.0047 in OVCA433, **P = 0.0036 in SKOV3, ***P = 0.0004 in TNBC-R no. 6, ***P = 0.0002 in TNBC-R no. 15. c, PARP inhibitor (PAPRi, □) versus PARP inhibitor + ALK inhibitor (PARPi + ALKi, ■): ***P = 0.0003 in OVCA433, *P = 0.0235 in SKOV3, **P = 0.0032 in TNBC-R no. 6, ***P = 0.0002 in TNBC-R no. 15; ALK inhibitor (ALKi, ●) versus PARP inhibitor + ALK inhibitor (PARPi + ALKi, ■): **P = 0.0016 in OVCA433, **P = 0.005 in SKOV3, **P = 0.0032 in TNBC-R no. 6, ***P = 0.0005 in TNBC-R no. 15.