PMID- 24239472
OWN - NLM
STAT- MEDLINE
DCOM- 20141229
LR  - 20211203
IS  - 1873-2496 (Electronic)
IS  - 1078-1439 (Linking)
VI  - 32
IP  - 1
DP  - 2014 Jan
TI  - Precision medicine for metastatic renal cell carcinoma.
PG  - 5-15
LID - S1078-1439(13)00301-3 [pii]
LID - 10.1016/j.urolonc.2013.07.010 [doi]
AB  - OBJECTIVES: This review provides a broad overview of emerging data that provide 
      hope that rational precision medicine for metastatic renal cell carcinoma (RCC) 
      may be possible. METHODS: PubMed and major conferences were searched for studies 
      reporting potential predictive biomarkers for the therapy of metastatic RCC. 
      RESULTS: The availability of multiple new agents for the therapy of advanced RCC 
      poses new challenges in terms of optimal selection of patients for the 
      appropriate drug. Prognostic stratification based on routine histopathologic, 
      clinical and laboratory factors have been utilized to broadly select individuals 
      based, i.e. high-dose interleukin (IL)-2 or vascular endothelial growth factor 
      (VEGF) inhibitors for good and intermediate risk patients and temsirolimus for 
      poor risk patients. While multiple candidate predictive molecular biomarkers 
      suggest that rational selection of patients for high-dose interleukin (IL)-2, and 
      VEGF and mammalian target of rapamycin (mTOR) inhibitors may be possible, none 
      have been validated for use in the clinic. Tumor heterogeneity and 
      standardization of tissue collection and analysis are massive challenges that 
      need to be addressed. Predictive molecules derived from tumor tissue, plasma and 
      host tissue may all be predictive for therapeutic benefit. Moreover, gene 
      expression may be modulated by multiple factors including epigenetics, 
      transcription factors and post-transcriptional and post-translational 
      modifications. Indeed, study of the interaction of molecular factors from all of 
      these sources with environmental and clinical factors may be necessary to develop 
      a unified profile composed of a panel of factors predictive of benefit from 
      specific agents (i.e. sustained response, limited toxicity and overall a positive 
      benefit/risk ratio). CONCLUSIONS: Conducting clinical trials with 1) prospective 
      incorporation of promising candidate predictive molecular biomarkers, 2) novel 
      biomarkers endpoints, and 3) mandatory biopsies of metastatic sites at different 
      time points on therapy, are potential important steps in developing the concept 
      of "the right medication for the right patient".
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Sonpavde, Guru
AU  - Sonpavde G
AD  - Urologic Medical Oncology, UAB Comprehensive Cancer Center, Birmingham, AL.
FAU - Choueiri, Toni K
AU  - Choueiri TK
AD  - Kidney Cancer Center, Dana-Farber Cancer Institute, Boston, MA; Department of 
      Medicine, Brigham and Women's Hospital Harvard Medical School, Boston, MA. 
      Electronic address: Toni_Choueiri@dfci.harvard.edu.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20131113
PL  - United States
TA  - Urol Oncol
JT  - Urologic oncology
JID - 9805460
RN  - 0 (Biomarkers)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Interleukin-2)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Biomarkers
MH  - Biomarkers, Tumor
MH  - Carcinoma, Renal Cell/*drug therapy/genetics
MH  - Clinical Trials as Topic
MH  - Comorbidity
MH  - Humans
MH  - Interleukin-2/antagonists & inhibitors
MH  - Kidney Neoplasms/*drug therapy/genetics
MH  - Neoplasm Metastasis/*drug therapy/genetics
MH  - Prognosis
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors
MH  - Vascular Endothelial Growth Factor A/antagonists & inhibitors
OTO - NOTNLM
OT  - Biomarkers
OT  - Predictive
OT  - Prognostic
OT  - Renal cell carcinoma
EDAT- 2013/11/19 06:00
MHDA- 2014/12/30 06:00
CRDT- 2013/11/19 06:00
PHST- 2013/05/13 00:00 [received]
PHST- 2013/07/04 00:00 [revised]
PHST- 2013/07/15 00:00 [accepted]
PHST- 2013/11/19 06:00 [entrez]
PHST- 2013/11/19 06:00 [pubmed]
PHST- 2014/12/30 06:00 [medline]
AID - S1078-1439(13)00301-3 [pii]
AID - 10.1016/j.urolonc.2013.07.010 [doi]
PST - ppublish
SO  - Urol Oncol. 2014 Jan;32(1):5-15. doi: 10.1016/j.urolonc.2013.07.010. Epub 2013 
      Nov 13.