title: Prognostic markers in renal cell carcinoma: A focus on the 'mammalian target of rapamycin' pathway.
abstract: OBJECTIVE
  Increased knowledge about the molecular pathways involved in tumorigenesis has led to the discovery of new prognostic molecular markers and development of novel targeted therapies for renal cell carcinoma (RCC). In this review we describe the prognostic markers of RCC and highlight the areas of recent discovery with a focus on the mammalian target of rapamycin (mTOR) pathway.
  
  
  METHODS
  We reviewed previous reports, using PubMed with the search terms 'renal cell carcinoma', 'molecular markers', 'prognosis', 'outcomes' and 'mammalian target of rapamycin pathway' published in the last two decades. We created a library of 100 references and focused on presenting the recent advances in the field.
  
  
  RESULTS
  Growing evidence suggests that mTOR deregulation is associated with many types of human cancer, including RCC. Consequently, temsirolimus and everolimus, which target mTOR, are approved for treating advanced RCC. There is a demand to integrate clinical, pathological and molecular markers into accurate prognostic models to provide patients with the most personalised cancer care possible.
  
  
  CONCLUSIONS
  The mTOR pathway is highly implicated in RCC tumorigenesis and progression, and its constituents might represent a promising prognostic tool and target for treating RCC. Combining newly discovered molecular markers with classic clinicopathological prognostics might potentially improve the management of RCC.
authors.affiliation: Division of Urologic Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Ramy F
authors.initials: RF
authors.lastname: Youssef
authors.affiliation: Division of Urologic Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Cost
authors.affiliation: Division of Urologic Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Oussama M
authors.initials: OM
authors.lastname: Darwish
authors.affiliation: Division of Urologic Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Margulis
keywords: 4E-BP1, eukaryotic initiation factor-binding protein-1; CA-9, carbonic anhydrase 9; HIF, hypoxia inducible factor; IRS-1, insulin receptor substrate-1; LDH, lactate dehydrogenase; Molecular markers; PI3k, phosphatidylinositol 3-kinase; Prognostic; Renal cell carcinoma; S6K1, S6 kinase 1; TKR, tyrosine kinase receptor; TSC, tuberous sclerosis complex; VEGF, vascular endothelial growth factor; VHL, von Hippel-Lindau; mTOR; mTOR, mammalian target of rapamycin