CCT196969 effectively inhibits growth and survival of melanoma brain metastasis cells.

Melanomas frequently metastasize to the brain. Despite recent progress in the treatment of melanoma brain metastasis, therapy resistance and relapse of disease remain unsolved challenges. CCT196969 is an SFK and pan-RAF inhibitor with documented effects in primary melanoma cell lines in vitro and in vivo. Using in vitro cell line assays, we studied the effects of CCT196969 in multiple melanoma brain metastasis cell lines. The drug effectively inhibited proliferation, migration, and survival in all examined cell lines, with a viability IC50 dose of 0.7-2.6 μM. Western blot analysis revealed decreased expression of p-ERK, p-MEK, p-STAT3 and STAT3 upon CCT196969 treatment, suggesting its impact on multiple important signalling pathways in melanoma brain metastasis. Furthermore, CCT196969 inhibited viability in a BRAF inhibitor resistant cell line. Our findings are in line with previous studies on the effects of CCT196969 in primary melanoma and reveal promising effects in melanoma brain metastasis cell lines. Further in vivo studies should be performed to determine the treatment potential of CCT196969 in patients with treatment naïve and resistant melanoma brain metastasis.