In:
PLOS ONE, Public Library of Science (PLoS), Vol. 17, No. 9 ( 2022-9-9), p. e0273711-
Abstract:
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 a SRC family kinase (SFK) and Raf proto-oncogene, serine/threonine kinase (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 viability IC 50 doses in the range of 0.18–2.6 μM. Western blot analysis showed decreased expression of p-ERK, p-MEK, p-STAT3 and STAT3 upon CCT196969 treatment. Furthermore, CCT196969 inhibited viability in two B-Raf Proto-Oncogene (BRAF) inhibitor resistant metastatic melanoma 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.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0273711
DOI:
10.1371/journal.pone.0273711.g001
DOI:
10.1371/journal.pone.0273711.g002
DOI:
10.1371/journal.pone.0273711.g003
DOI:
10.1371/journal.pone.0273711.g004
DOI:
10.1371/journal.pone.0273711.g005
DOI:
10.1371/journal.pone.0273711.g006
DOI:
10.1371/journal.pone.0273711.g007
DOI:
10.1371/journal.pone.0273711.s001
DOI:
10.1371/journal.pone.0273711.s002
DOI:
10.1371/journal.pone.0273711.s003
DOI:
10.1371/journal.pone.0273711.s004
DOI:
10.1371/journal.pone.0273711.s005
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2267670-3
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