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. 2021 Jul 21;218(9):e20210571. doi: 10.1084/jem.20210571

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© 2021 Vendramin et al.

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Figure 3. — Tigecycline overcomes acquired resistance to MAPK inhibitors in vivo and significantly increases survival. (A) Tumor volume of cohorts of Mel-015 BRAF^V600 PDX mice treated with vehicle (DMSO, n = 9), tigecycline (n = 8), DT (n = 9), DTT (n = 10), or DT with the addition of tigecycline at MRD (DT + T, n = 5). Data are mean ± SEM of different biological replicates. ****, P < 0.0001 by two-way ANOVA. One of the mice in the DT + T cohort had to be euthanized on day 76, thereby explaining the rapid drop in the growth curve. (B) Kaplan–Meier plot showing PFS of mice described in A. DT (n = 4), DTT (n = 10), DT with the addition of tigecycline at MRD (DT + T, n = 5). NS, P > 0.05; **, P < 0.01 by log-rank (Mantel–Cox) test. (C) Tumor volume of cohorts of Mel-006 BRAF^V600E PDX mice treated with vehicle (DMSO, n = 5), dabrafenib (D, n = 3), tigecycline, DT (n = 6), dabrafenib + tigecycline (D + Tige, n = 7), or DTT (n = 14). Data are mean ± SEM of different biological replicates. ****, P < 0.0001 by two-way ANOVA. Two mice in the D + T cohort had to be euthanized between day 110 and 120, thereby explaining the rapid drop in the growth curve. (D) Kaplan–Meier plot showing PFS of mice described in C. DT (n = 6), dabrafenib + tigecycline (D + Tige, n = 7), DTT (n = 14). **, P < 0.01; ****, P < 0.0001 by log-rank (Mantel–Cox) test.