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. 2020 Jul 3;22(9):376–389. doi: 10.1016/j.neo.2020.06.006

Fig. 1.

Fig. 1

The genetic suppression of BRAF increases survival in BRAFVE, Cdkn2a, and Pten mutant melanomas. (A) Kaplan–Meier percent survival curves for mice with BRAF tumors. Dct::TVA; BRAFCA/CACdkn2alox/lox; Ptenlox/lox mice were injected with viruses encoding Cre (black line, n = 21, tumor incidence 21/21) or Dct::TVA; Cdkn2alox/lox; Ptenlox/lox mice injected with viruses encoding BRAFV600E+Cre (red line, n = 15, tumor incidence 15/15). No significant difference was observed between the BRAFCA/CA and BRAFV600E tumors,P = 0.0523. No tumors developed in Dct::TVA; Cdkn2alox/lox; Ptenlox/lox mice injected with Cre alone as controls (Control A, blue line, n = 17, tumor incidence 0/17). (B) Kaplan–Meier percent survival curves comparing TRE-BRAFVE tumors with BRAFV600E tumors. Dct::TVA; Cdkn2alox/lox; Ptenlox/lox mice were injected with viruses encoding Cre (black line, n = 15 tumor incidence, 15/15) or Dct::TVA; Cdkn2alox/lox; Ptenlox/lox mice injected with viruses encoding BRAFV600E+Cre+Tet-Off (red line, n = 8, tumor incidence 8/8). No significant difference was observed between the TRE-BRAFVE and BRAFV600E tumors,P = 0.504. (C) Kaplan–Meier percent survival curves comparing TRE-BRAFVE tumors compared with BRAFCA/CA tumors. Dct::TVA; BRAFCA/CACdkn2alox/lox; Ptenlox/lox mice were injected with viruses encoding Cre (black line, n = 21 tumor incidence, 21/21); or Dct::TVA; Cdkn2alox/lox; Ptenlox/lox mice injected with viruses encoding TRE-BRAFV600E+Cre+Tet-Off (red line, n = 8, tumor incidence 8/18). No significant difference was observed between the BRAFCA/CAand BRAFV600E tumors,P = 0.135. No tumors developed in Dct::TVA; Cdkn2alox/lox; Ptenlox/lox mice injected with Cre+TRE-BRAFVE in the absence of Tet-Off as controls (n = 11, tumor incidence 0/11). (D) Kaplan–Meier survival curves demonstrating the effect of genetic BRAFVE inhibition. Dct::TVA;Cdkn2alox/lox; Ptenlox/lox mice were injected with viruses encoding Tet-Off+Cre+TRE-BRAFVE. Mice were monitored for tumor formation and randomized to receive either a Dox diet or control diet when tumors were measured at 1.0  cm3 (Dox diet dotted line, n = 14, control diet dashed line, n = 8). A significant increase in survival was found between Dox-treated and control mice (P = 0.0000017).