Abstract | BACKGROUND: Metastatic bladder cancer is a serious condition with a 5-year survival rate of approximately 14 %, a rate that has remained unchanged for almost three decades. Thus, there is a profound need to identify the driving mutations for these aggressive tumors to better determine appropriate treatments. Mutational analyses of clinical samples suggest that mutations in either the phosphoinositide-3 kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) or RAS/MEK/ERK pathways drive bladder cancer progression, although it remains to be tested whether the inhibition of either (or both) of these pathways can arrest PI3K/mTOR- or Ras-driven proliferation. METHODS: Herein, we used several bladder cancer cell lines to determine drug sensitivity according to genetic background and also studied mouse models of engrafted UM-UC-3 cells and patient-derived xenografts (PDXs) to test PI3K/mTOR and MEK inhibition in vivo. RESULTS: CONCLUSION:
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Authors | Pasquale Cirone, Catharine J Andresen, Jeetendra R Eswaraka, Patrick B Lappin, Cedo M Bagi |
Journal | Cancer chemotherapy and pharmacology
(Cancer Chemother Pharmacol)
Vol. 73
Issue 3
Pg. 525-38
(Mar 2014)
ISSN: 1432-0843 [Electronic] Germany |
PMID | 24442130
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 2-amino-8-(4-(2-hydroxyethoxy)cyclohexyl)-6-(6-methoxypyridin-3-yl)-4-methylpyrido(2,3-d)pyrimidin-7(8H)-one
- Benzamides
- Phosphoinositide-3 Kinase Inhibitors
- Protein Kinase Inhibitors
- Pyridones
- Pyrimidines
- mirdametinib
- Diphenylamine
- MTOR protein, human
- TOR Serine-Threonine Kinases
- MAP Kinase Kinase Kinases
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Topics |
- Aged, 80 and over
- Animals
- Antineoplastic Combined Chemotherapy Protocols
(pharmacology)
- Benzamides
(administration & dosage, pharmacology)
- Diphenylamine
(administration & dosage, analogs & derivatives, pharmacology)
- Disease Models, Animal
- Female
- Humans
- MAP Kinase Kinase Kinases
(antagonists & inhibitors, genetics, metabolism)
- MAP Kinase Signaling System
(drug effects)
- Mice
- Mice, Inbred NOD
- Mice, SCID
- Phosphatidylinositol 3-Kinases
(genetics, metabolism)
- Phosphoinositide-3 Kinase Inhibitors
- Protein Kinase Inhibitors
(administration & dosage, pharmacology)
- Pyridones
(administration & dosage, pharmacology)
- Pyrimidines
(administration & dosage, pharmacology)
- Random Allocation
- TOR Serine-Threonine Kinases
(antagonists & inhibitors, genetics, metabolism)
- Urinary Bladder Neoplasms
(drug therapy, enzymology, genetics, pathology)
- Xenograft Model Antitumor Assays
(methods)
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