Identification of the Serine Biosynthesis Pathway as a Critical Component of BRAF Inhibitor Resistance of Melanoma, Pancreatic, and Non-Small Cell Lung Cancer Cells

Metastatic melanoma cells commonly acquire resistance to V600E inhibitors (BRAFi). In this study, we identified serine biosynthesis as a critical mechanism of resistance. Proteomic assays revealed differential protein expression of serine biosynthetic enzymes PHGDH, PSPH, and PSAT1 following vemuraf...

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Veröffentlicht in:	Molecular cancer therapeutics 2017-08, Vol.16 (8), p.1596-1609
Hauptverfasser:	Ross, Kayleigh C, Andrews, Andrew J, Marion, Christopher D, Yen, Timothy J, Bhattacharjee, Vikram
Format:	Artikel
Sprache:	eng
Schlagworte:	Biosynthesis Biosynthetic Pathways - drug effects Biotechnology Cancer Carcinoma, Non-Small-Cell Lung - drug therapy Carcinoma, Non-Small-Cell Lung - pathology Cell Line, Tumor Cell Proliferation - drug effects Deoxycytidine - analogs & derivatives Deoxycytidine - pharmacology Deoxycytidine - therapeutic use Deoxyribonucleic acid DNA DNA damage Drug resistance Drug Resistance, Neoplasm - drug effects Folic acid Gemcitabine Humans Imidazoles - pharmacology Imidazoles - therapeutic use Indoles - pharmacology Indoles - therapeutic use Inhibitors Lung cancer Lung Neoplasms - drug therapy Lung Neoplasms - pathology Melanoma Melanoma - drug therapy Melanoma - pathology Metastases Methotrexate Methotrexate - pharmacology Methotrexate - therapeutic use Models, Biological Oximes - pharmacology Oximes - therapeutic use Pancreatic cancer Pancreatic Neoplasms - drug therapy Pancreatic Neoplasms - pathology Phosphoglycerate Dehydrogenase - metabolism Proto-Oncogene Proteins B-raf - antagonists & inhibitors Proto-Oncogene Proteins B-raf - metabolism Serine Serine - metabolism siRNA Sulfonamides - pharmacology Sulfonamides - therapeutic use Tumor cell lines Tumor cells Vemurafenib
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