CCT196969 and CCT241161 Inhibit SFK in Patient-Derived Resistant Cells
(A) A375 cell colony formation with DMSO, PLX4720, CCT196969, or CCT241161 (0.5 μM) after 7 or 20 days.
(B) A375/R cell proliferation assay (CellTiter Glo) with PLX4720, CCT196969, and CCT241161.
(C) A375/R xenograft growth in nude mice treated with vehicle, PLX4720, CCT196969, or CCT241161. ∗∗∗p ≤ 0.001 (t test, two-tailed).
(D) Patient #1 PDX growth in NSG mice treated with PLX4720.
(E) Growth of PLX4720-resistant PDX from patient #1, from (D), in mice treated with PLX4720, CCT196969, or CCT241161 7 days after cell injection. ∗∗∗p ≤ 0.001 (t test, two-tailed).
(F) Patient #2 cell proliferation assay (CellTiter Glo) with PLX4720, CCT196969, or CCT241161.
(G) RPPA quantification for pMEK, pERK, and pSFK in three vemurafenib-resistant patient-derived cell lines treated with DMSO (vehicle), PLX4720, CCT196969, and CCT241161 (1 μM; 4 hr).
(H) pMEK, pERK, ERK2, pSFK, and SRC in patient #2 cells treated with DMSO, PLX4720, CCT196969, or CCT241161 (1 μM; 4 hr).
(I) PARP and caspase 3 in patient #2 cells treated with DMSO, PLX4720, CCT196969, or CCT241161 (1 μM; 4 hr).
(J) Patient #2 cell xenograft growth in nude mice treated with vehicle, PLX4720, CCT196969, or CCT241161 16 days after tumor implant. ∗∗∗p ≤ 0.001 (t test, two-tailed).
Bars represent SEM. See also Figure S3 and Tables S4 and S5.