PMID- 21791089
OWN - NLM
STAT- MEDLINE
DCOM- 20111209
LR  - 20211203
IS  - 1476-4598 (Electronic)
IS  - 1476-4598 (Linking)
VI  - 10
DP  - 2011 Jul 26
TI  - Targeting renal cell carcinoma with NVP-BEZ235, a dual PI3K/mTOR inhibitor, in 
      combination with sorafenib.
PG  - 90
LID - 10.1186/1476-4598-10-90 [doi]
AB  - BACKGROUND: Targeted therapies for metastatic renal cell carcinoma (RCC), 
      including mammalian target of rapamycin (mTOR) inhibitors and small-molecule 
      multikinase inhibitors, have produced clinical effects. However, most patients 
      acquire resistance over time. Thus, new therapeutic strategies need to be 
      developed. Here, we evaluated the effect of the dual PI3K/mTOR inhibitor 
      NVP-BEZ235, in combination with the multikinase inhibitor sorafenib on renal 
      cancer cell proliferation and survival in vitro as well as on tumor growth in 
      vivo. METHODS: The renal carcinoma cell lines 786-0 and Caki-1 were treated with 
      NVP-BEZ235 or sorafenib, either alone or in combination. Tumor cell proliferation 
      and apoptosis were investigated in vitro. The anticancer efficacy of NVP-BEZ235 
      alone, or in combination with sorafenib, was also evaluated on RCC xenografts in 
      nude mice. RESULTS: Treatment of 786-0 and Caki-1 cells with NVP-BEZ235 or 
      sorafenib resulted in reduced tumor cell proliferation and increased tumor cell 
      apoptosis in vitro. The combination of NVP-BEZ235 and sorafenib was more 
      effective than each compound alone. Similarly, in vivo, NVP-BEZ235 or sorafenib 
      reduced the growth of xenografts generated from 786-0 or Caki-1 cells. The 
      antitumor efficacy of NVP-BEZ235 in combination with sorafenib was superior to 
      NVP-BEZ235 or sorafenib alone. CONCLUSIONS: Our findings indicate that the 
      simultaneous use of NVP-BEZ235 and sorafenib has greater antitumor benefit 
      compared to either drug alone and thus provides a treatment strategy in RCC.
FAU - Roulin, Didier
AU  - Roulin D
AD  - Department of Visceral Surgery, Centre Hospitalier Universitaire Vaudois and 
      University of Lausanne, Pavillon 3, Av, de Beaumont, 1011 Lausanne, Switzerland.
FAU - Waselle, Laurent
AU  - Waselle L
FAU - Dormond-Meuwly, Anne
AU  - Dormond-Meuwly A
FAU - Dufour, Marc
AU  - Dufour M
FAU - Demartines, Nicolas
AU  - Demartines N
FAU - Dormond, Olivier
AU  - Dormond O
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110726
PL  - England
TA  - Mol Cancer
JT  - Molecular cancer
JID - 101147698
RN  - 0 (Benzenesulfonates)
RN  - 0 (Imidazoles)
RN  - 0 (Phenylurea Compounds)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyridines)
RN  - 0 (Quinolines)
RN  - 25X51I8RD4 (Niacinamide)
RN  - 9ZOQ3TZI87 (Sorafenib)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - RUJ6Z9Y0DT (dactolisib)
SB  - IM
MH  - Animals
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Benzenesulfonates/*administration & dosage
MH  - Carcinoma, Renal Cell/*drug therapy/pathology
MH  - Cell Line, Tumor
MH  - Female
MH  - Humans
MH  - Imidazoles/*administration & dosage
MH  - Kidney Neoplasms/*drug therapy/pathology
MH  - Mice
MH  - Mice, Nude
MH  - Molecular Targeted Therapy
MH  - Niacinamide/analogs & derivatives
MH  - Phenylurea Compounds
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Protein Kinase Inhibitors/administration & dosage
MH  - Pyridines/*administration & dosage
MH  - Quinolines/*administration & dosage
MH  - Sorafenib
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors
MH  - Treatment Outcome
MH  - Xenograft Model Antitumor Assays
PMC - PMC3160413
EDAT- 2011/07/28 06:00
MHDA- 2011/12/14 06:00
PMCR- 2011/07/26
CRDT- 2011/07/28 06:00
PHST- 2010/12/17 00:00 [received]
PHST- 2011/07/26 00:00 [accepted]
PHST- 2011/07/28 06:00 [entrez]
PHST- 2011/07/28 06:00 [pubmed]
PHST- 2011/12/14 06:00 [medline]
PHST- 2011/07/26 00:00 [pmc-release]
AID - 1476-4598-10-90 [pii]
AID - 10.1186/1476-4598-10-90 [doi]
PST - epublish
SO  - Mol Cancer. 2011 Jul 26;10:90. doi: 10.1186/1476-4598-10-90.