Abstract
Even though activating mutations of B-Raf, a kinase atop the MAPK signaling cascade, reportedly sensitize tumor cells to MEK inhibitors, Raf and MEK inhibitors have exhibited limited clinical activity. In this issue of the JCI, Cragg et al. report that MEK inhibition upregulates the proapoptotic Bcl-2 family member Bim but induces little regression of human melanoma xenografts in mice unless the Bcl-2 antagonist ABT-737 is added (see the related article beginning on page 3651). These findings illustrate the potential benefit of simultaneously inhibiting oncogenic kinases and inhibiting Bcl-2 action in solid tumors.
Publication types
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Research Support, N.I.H., Extramural
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Comment
MeSH terms
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Animals
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Apoptosis Regulatory Proteins / antagonists & inhibitors*
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Apoptosis Regulatory Proteins / genetics
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Bcl-2-Like Protein 11
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Biphenyl Compounds
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Humans
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Melanoma / genetics*
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Melanoma / pathology
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Membrane Proteins / antagonists & inhibitors*
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Membrane Proteins / genetics
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Mice
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Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors*
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Mitogen-Activated Protein Kinase Kinases / genetics
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Models, Biological
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Nitrophenols
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Piperazines
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Proto-Oncogene Proteins / antagonists & inhibitors*
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins B-raf / antagonists & inhibitors*
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Proto-Oncogene Proteins B-raf / genetics
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Skin Neoplasms / genetics*
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Skin Neoplasms / pathology
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Sulfonamides
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Xenograft Model Antitumor Assays
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bcl-2 Homologous Antagonist-Killer Protein / genetics
Substances
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ABT-737
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Apoptosis Regulatory Proteins
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BCL2L11 protein, human
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Bcl-2-Like Protein 11
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Bcl2l11 protein, mouse
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Biphenyl Compounds
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Membrane Proteins
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Nitrophenols
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Piperazines
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Proto-Oncogene Proteins
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Sulfonamides
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bcl-2 Homologous Antagonist-Killer Protein
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Proto-Oncogene Proteins B-raf
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Mitogen-Activated Protein Kinase Kinases