Synergistic melanoma cell death mediated by inhibition of both MCL1 and BCL2 in high-risk tumors driven by NF1/PTEN loss

Melanomas driven by loss of the NF1 tumor suppressor have a high risk of treatment failure and effective therapies have not been developed. Here we show that loss-of-function mutations of nf1 and pten result in aggressive melanomas in zebrafish, representing the first animal model of NF1-mutant mela...

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Veröffentlicht in:	Oncogene 2021-09, Vol.40 (38), p.5718-5729
Hauptverfasser:	He, Shuning, Zimmerman, Mark W., Layden, Hillary M., Berezovskaya, Alla, Etchin, Julia, Martel, Megan W., Thurston, Grace, Jing, Chang-Bin, van Rooijen, Ellen, Kaufman, Charles K., Rodig, Scott J., Zon, Leonard I., Patton, E. Elizabeth, Mansour, Marc R., Look, A. Thomas
Format:	Artikel
Sprache:	eng
Schlagworte:	1-Phosphatidylinositol 3-kinase 13/2 13/51 13/95 14/35 14/63 631/67/1813/1634 631/67/70 64/116 96/106 Animal models Animals Antimitotic agents Antineoplastic agents Apoptosis Autophagy Bridged Bicyclo Compounds, Heterocyclic - administration & dosage Bridged Bicyclo Compounds, Heterocyclic - pharmacology Cancer Care and treatment Cell Biology Cell death Cell Line, Tumor Cell Proliferation - drug effects Cell Survival - drug effects Danio rerio Development and progression Drug Synergism Drug therapy, Combination Everolimus - administration & dosage Everolimus - pharmacology Genetic aspects Human Genetics Humans Internal Medicine Loss of Function Mutation Mcl-1 protein Medicine Medicine & Public Health Melanoma Melanoma - drug therapy Melanoma - genetics Melanoma - pathology MTOR Inhibitors - administration & dosage MTOR Inhibitors - pharmacology Myeloid Cell Leukemia Sequence 1 Protein - antagonists & inhibitors Neurofibromin 1 - genetics Oncology Oncology, Experimental Phagocytosis Proto-Oncogene Proteins c-bcl-2 - antagonists & inhibitors PTEN Phosphohydrolase - genetics PTEN protein Pyrimidines - administration & dosage Pyrimidines - pharmacology Rapamycin Sirolimus - administration & dosage Sirolimus - analogs & derivatives Sirolimus - pharmacology Sulfonamides - administration & dosage Sulfonamides - pharmacology Thiophenes - administration & dosage Thiophenes - pharmacology TOR protein Toxicity Tumor suppressor genes Tumors Xenograft Model Antitumor Assays Zebrafish
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