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Fig. 3 | Breast Cancer Research

Fig. 3

From: A phase II clinical trial of the Aurora and angiogenic kinase inhibitor ENMD-2076 for previously treated, advanced, or metastatic triple-negative breast cancer

Fig. 3

Effects of ENMD-2076 on pharmacodynamic markers in serial tumor biopsies obtained in a subset of patients. a Paired samples were available for eight patients at baseline prior to dosing (C1D1) and postdose on days 14–16 (C1D15). An additional sample was obtained in one patient who experienced stable disease for ten cycles followed by progression (end of treatment [EOT]). Tissue was analyzed by IHC for Ki-67 as a marker of cellular proliferation. b Nonresponder. Staining was performed as in panel a. Note that there is no decrease in proliferation or increase in apoptosis in the nonresponder following ENMD-2076 treatment. Samples were analyzed by IHC for CD34 expression as a marker of microvessel density. Changes were independent of tumor response and clinical benefit to ENMD-2076 treatment. Patients 01-005, 01-030, 02-004, 02-006, 02-012, and 02-027 had progressive disease (PD) at first imaging assessment following two cycles; 01-028 had stable disease (SD) for ten cycles; and 01-031 had SD for four cycles. c Immunoflurorescence analysis of tumor biopsies for 4′,6-diamidino-2-phenylindole (DAPI), p53, and p73 in a patient who had stable disease by Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) after two cycles of treatment and then progressed after cycle 3. Patient has a p53 mutation R273S. Note an increase in p53 and p73 following treatment, which is consistent with preclinical findings in patient-derived tumor xenograft models. IHC images from 01-028 responder. Cleaved caspase 3, Ki-67, and CD34 on serial tumor biopsies were used to assess apoptosis, proliferation, and microvessel density, respectively, in a patient responding to ENMD-2076 treatment with prolonged stable disease for ten cycles. Biopsies were obtained prior to treatment, 15 days after treatment, and at the time of disease progression day 280. Formalin-fixed, paraffin-embedded tissue sections were stained with the indicated antibodies, and representative images were obtained at × 20 magnification. Note an increase in cleaved caspase 3 and a decrease in Ki-67 and CD34 in the posttreatment biopsy. At the time of disease progression, these changes were reversed. Changes in (d) Ki-67 and (e) CD34 (microvessel density) in serial tumor biopsies. Baseline and day 15 samples were available for eight patients. An additional sample was obtained from one patient at the time of progression following prolonged stable disease. Ki-67 and CD34 were assessed using IHC. SA-β-gal Senescence-associated β-galactosidase

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