Extended Data Fig. 5: FPS-ZM1 radiosensitizes experimental and human brain metastases.

a, Schema of experimental design. E0771-BrM were inoculated IC into C57BL/6 mice and three days later mice received 10 doses of 3 Gy WBRT plus 500 mg/Kg/day FPS-ZM1 or vehicle until the end of the experiment. Intracranial tumor growth was measured ex vivo at the end of the experiment. b, Representative bioluminescence images of ex vivo brains of control and experimental arms at endpoint, 2 weeks after IC injection. c, Quantification of ex vivo photon flux values from brains from mice inoculated with E0771-BrM that received WBRT plus vehicle or FPS-ZM1, as depicted in (a). Values are shown in box-and-whisker plots where every dot represents a different brain and the line in the box corresponds to the median. The boxes go from the upper to the lower quartiles and the whiskers go from the minimum to the maximum value (n = 10, Vehicle + γ-IR; n = 11, FPS-ZM1 + γ-IR). P value was calculated using two-tailed t test. d, Representative S100A9 immunofluorescence from two human brain metastasis that were processed as PDOCs. Patient#1 corresponds to a previously untreated brain metastasis that was negative for S100A9. Patient#2 corresponds to a relapsed metastasis. Scale bar: 50 µm. e, Quantification of BrdU+ cancer cells in PDOC from patient#1 treated with FPS-ZM1 and/or γ-IR. Values are shown in box-and-whisker plots where every dot represents an independent culture and the line in the box corresponds to the median. The boxes go from the upper to the lower quartiles and the whiskers go from the minimum to the maximum value (n = 11, DMSO; n = 9, FPS-ZM1; n = 10, γ-IR; n = 9, FPS-ZM1 + γ-IR). P value was calculated using two-tailed t test. f, Quantification of percentage of time mice from different groups spent in open or closed arms in the elevated plus maze. Values are shown in a scatter dot plot where every dot represents a mouse and the line corresponds to the mean (n = 6, Control; n = 13, Vehicle + γ-IR, n = 20, FPS-ZM1 + γ-IR). Calculation of P values are detailed in Supplementary Table 24. g, Quantification of freezing time comparing different groups when trained (acquisition), when they were tested for the association between the context and the mild electric shock, recalling the information during the short-term trial, and when a substantial change of context was used to test a reduction in the behavior (Context change trial). Values are shown in a scatter dot plot where every dot represents a mouse and the line corresponds to the mean (n = 6, Control; n = 13, Vehicle + γ-IR, n = 20, FPS-ZM1 + γ-IR). Calculation of P values are detailed in Supplementary Table 24. h, Quantification of the brains long T2 component by ex vivo ultrahigh-field MRI in brains from experiment depicted in Fig. 6i. Values are shown in box-and-whisker plots where every dot represents a brain and the line in the box corresponds to the median. The boxes go from the upper to the lower quartiles and the whisker go from the minimum to the maximum value (n = 5, each experimental condition). P value was calculated using two-tailed t test.