PMID- 17935273
OWN - NLM
STAT- MEDLINE
DCOM- 20071121
LR  - 20211203
IS  - 1107-0625 (Print)
IS  - 1107-0625 (Linking)
VI  - 12 Suppl 1
DP  - 2007 Sep
TI  - Sunitinib, sorafenib and mTOR inhibitors in renal cancer.
PG  - S151-62
AB  - Understanding the alterations in cellular protein interactions and their 
      relations to genetic mutations that cause renal cell carcinoma (RCC) provides a 
      unique opportunity for the development of disease-specific therapy for patients 
      with advanced forms of this disease. There is substantial evidence of an 
      association between mutation on von Hippel-Lindau (VHL) gene and the earliest 
      stages of tumorigenesis of RCC. The main consequence of VHL loss is the 
      upregulation of downstream proangiogenic factors leading to highly vascular 
      tumors. Overexpression of hypoxia inducible factor (HIF) is also caused by the 
      mammalian target of rapamycin (mTOR), a key component of signaling pathways 
      inside the cell, involved in cell proliferation. The inhibition of proangiogenic 
      factors and mTOR was the main idea behind the development of new targeted agents 
      in advanced RCC. Since December 2005, 3 targeted agents have been approved by the 
      U.S. Food and Drug Administration (FDA) for the treatment of advanced RCC: 
      sorafenib, sunitinib and temsirolimus. Sorafenib and sunitinib are synthetic, 
      orally active agents shown to directly inhibit vascular endothelial growth factor 
      receptors -2 and -3 (VEGFR-2, VEGFR-3) and platelet-derived growth factor 
      receptor beta (PDGFR-beta), while temsirolimus is an mTOR inhibitor. Recent 
      clinical studies form the basis for new guidelines for the treatment of advanced 
      RCC: sorafenib should be used as a second-line treatment, sunitinib as the 
      first-line therapy for good and intermediate-risk patients, and temsirolimus 
      should be considered as first-line treatment for poor-risk patients. Future 
      approaches to targeted therapy should focus on optimizing the use of current 
      active drugs, exploring their combinations or investigating their sequential use. 
      In addition, it is important to define the mechanisms of resistance on their use 
      and to further investigate biomarkers and enhance treatment efficacy for the 
      individual patients. The development of these targeted therapies represents an 
      exciting step forward in the treatment of advanced RCC.
FAU - Radulovic, Sinisa
AU  - Radulovic S
AD  - Department of Translational Research, Institute for Oncology and Radiology of 
      Serbia, Belgrade, Serbia. sinisar@ncrc.ac.yu
FAU - Bjelogrlic, Snezana K
AU  - Bjelogrlic SK
LA  - eng
PT  - Journal Article
PT  - Review
PL  - Cyprus
TA  - J BUON
JT  - Journal of B.U.ON. : official journal of the Balkan Union of Oncology
JID - 100883428
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Benzenesulfonates)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Indoles)
RN  - 0 (Phenylurea Compounds)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyridines)
RN  - 0 (Pyrroles)
RN  - 25X51I8RD4 (Niacinamide)
RN  - 624KN6GM2T (temsirolimus)
RN  - 9HW64Q8G6G (Everolimus)
RN  - 9ZOQ3TZI87 (Sorafenib)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta)
RN  - EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - V99T50803M (Sunitinib)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Angiogenesis Inhibitors/pharmacology/*therapeutic use
MH  - Benzenesulfonates/pharmacology/*therapeutic use
MH  - Biomarkers, Tumor/genetics/metabolism
MH  - Carcinoma, Renal Cell/*drug therapy/enzymology/genetics/metabolism/pathology
MH  - Drug Resistance, Neoplasm
MH  - Everolimus
MH  - Humans
MH  - Indoles/pharmacology/*therapeutic use
MH  - Kidney Neoplasms/*drug therapy/enzymology/genetics/metabolism/pathology
MH  - Niacinamide/analogs & derivatives
MH  - Patient Selection
MH  - Phenylurea Compounds
MH  - Practice Guidelines as Topic
MH  - Protein Kinase Inhibitors/pharmacology/*therapeutic use
MH  - Protein Kinases/metabolism
MH  - Pyridines/pharmacology/*therapeutic use
MH  - Pyrroles/pharmacology/*therapeutic use
MH  - Receptor, Platelet-Derived Growth Factor beta/antagonists & inhibitors/metabolism
MH  - Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors/metabolism
MH  - Sirolimus/*analogs & derivatives/pharmacology/therapeutic use
MH  - Sorafenib
MH  - Sunitinib
MH  - TOR Serine-Threonine Kinases
MH  - Treatment Outcome
RF  - 103
EDAT- 2007/11/06 09:00
MHDA- 2007/12/06 09:00
CRDT- 2007/11/06 09:00
PHST- 2007/11/06 09:00 [pubmed]
PHST- 2007/12/06 09:00 [medline]
PHST- 2007/11/06 09:00 [entrez]
PST - ppublish
SO  - J BUON. 2007 Sep;12 Suppl 1:S151-62.