PMID- 31840081
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240422
IS  - 2397-768X (Print)
IS  - 2397-768X (Electronic)
IS  - 2397-768X (Linking)
VI  - 3
DP  - 2019
TI  - Synchronous inhibition of mTOR and VEGF/NRP1 axis impedes tumor growth and 
      metastasis in renal cancer.
PG  - 31
LID - 10.1038/s41698-019-0105-2 [doi]
LID - 31
AB  - Clear cell renal cell carcinoma (ccRCC) is known for its highly vascular 
      phenotype which is associated with elevated expression of vascular endothelial 
      growth factor A (VEGF), also known as vascular permeability factor (VPF). 
      Accordingly, VEGF has been an attractive target for antiangiogenic therapies in 
      ccRCC. Two major strategies have hitherto been utilized for VEGF-targeted 
      antiangiogenic therapies: targeting VEGF by antibodies, ligand traps or aptamers, 
      and targeting the VEGF receptor signaling via antibodies or small-molecule 
      tyrosine-kinase inhibitors (TKIs). In the present article we utilized two 
      entirely different approaches: targeting mammalian target of rapamycin (mTOR) 
      pathway that is known to be involved in VEGF synthesis, and disruption of 
      VEGF/Neuroplin-1 (NRP1) axis that is known to activate proangiogenic and 
      pro-tumorigenic signaling in endothelial and tumor cells, respectively. 
      Everolimus (E) and a small-molecule inhibitor EG00229 (G) were used for the 
      inhibition of mTOR and the disruption of VEGF/NRP1 axis, respectively. We also 
      exploited a liposomal formulation decorated with a proprietary 
      tumor-targeting-peptide (TTP) to simultaneously deliver these two agents in a 
      tumor-targeted manner. The TTP-liposomes encapsulating both Everolimus and 
      EG00229 (EG-L) demonstrated higher in vitro and in vivo growth retardation than 
      the single drug-loaded liposomes (E-L and G-L) in two different ccRCC models and 
      led to a noticeable reduction in lung metastasis in vivo. In addition, EG-L 
      displayed remarkable inhibition of tumor growth in a highly aggressive syngeneic 
      immune-competent mouse model of ccRCC developed in Balb/c mice. Taken together, 
      this study demonstrates an effective approach to achieve improved therapeutic 
      outcome in ccRCC.
CI  - (c) The Author(s) 2019.
FAU - Pal, Krishnendu
AU  - Pal K
AD  - Department of Biochemistry and Molecular Biology, Mayo Clinic Florida, 4500 San 
      Pablo Road S, Jacksonville, FL 32224 USA. ISNI: 0000 0004 0443 9942. GRID: 
      grid.417467.7
FAU - Madamsetty, Vijay Sagar
AU  - Madamsetty VS
AUID- ORCID: 0000-0001-9883-190X
AD  - Department of Biochemistry and Molecular Biology, Mayo Clinic Florida, 4500 San 
      Pablo Road S, Jacksonville, FL 32224 USA. ISNI: 0000 0004 0443 9942. GRID: 
      grid.417467.7
FAU - Dutta, Shamit Kumar
AU  - Dutta SK
AD  - Department of Biochemistry and Molecular Biology, Mayo Clinic Florida, 4500 San 
      Pablo Road S, Jacksonville, FL 32224 USA. ISNI: 0000 0004 0443 9942. GRID: 
      grid.417467.7
FAU - Wang, Enfeng
AU  - Wang E
AD  - Department of Biochemistry and Molecular Biology, Mayo Clinic Florida, 4500 San 
      Pablo Road S, Jacksonville, FL 32224 USA. ISNI: 0000 0004 0443 9942. GRID: 
      grid.417467.7
FAU - Angom, Ramcharan Singh
AU  - Angom RS
AD  - Department of Biochemistry and Molecular Biology, Mayo Clinic Florida, 4500 San 
      Pablo Road S, Jacksonville, FL 32224 USA. ISNI: 0000 0004 0443 9942. GRID: 
      grid.417467.7
FAU - Mukhopadhyay, Debabrata
AU  - Mukhopadhyay D
AD  - Department of Biochemistry and Molecular Biology, Mayo Clinic Florida, 4500 San 
      Pablo Road S, Jacksonville, FL 32224 USA. ISNI: 0000 0004 0443 9942. GRID: 
      grid.417467.7
LA  - eng
GR  - R01 CA078383/CA/NCI NIH HHS/United States
GR  - R01 CA150190/CA/NCI NIH HHS/United States
GR  - R29 CA078383/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20191205
PL  - England
TA  - NPJ Precis Oncol
JT  - NPJ precision oncology
JID - 101708166
PMC - PMC6895165
OTO - NOTNLM
OT  - Renal cell carcinoma
OT  - Targeted therapies
COIS- Competing interestsThe authors declare the following competing financial 
      interest(s): K.P., V.S.M., and D.M. have applied for protection of intellectual 
      property related to the results in the manuscript. There are no other conflicts 
      of interest to declare.
EDAT- 2019/12/17 06:00
MHDA- 2019/12/17 06:01
PMCR- 2019/12/05
CRDT- 2019/12/17 06:00
PHST- 2019/04/15 00:00 [received]
PHST- 2019/10/17 00:00 [accepted]
PHST- 2019/12/17 06:00 [entrez]
PHST- 2019/12/17 06:00 [pubmed]
PHST- 2019/12/17 06:01 [medline]
PHST- 2019/12/05 00:00 [pmc-release]
AID - 105 [pii]
AID - 10.1038/s41698-019-0105-2 [doi]
PST - epublish
SO  - NPJ Precis Oncol. 2019 Dec 5;3:31. doi: 10.1038/s41698-019-0105-2. eCollection 
      2019.