Renal cell carcinoma may adapt to and overcome anti-angiogenic intervention with thalidomide.
OBJECTIVE
To report on the failure of thalidomide to inhibit tumour growth in an animal model of human renal cell carcinoma (RCC).


METHODS
An orthotopic xenograft model of human RCC was used in which tumour cells were implanted in the left kidney of male 'severe combined immunodeficient' mice. Thalidomide was administered by intraperitoneal injection and after 34 days the mice were killed. The extent of tumour growth was compared in treated and untreated mice. Total RNA was extracted from both tumour-affected and contralateral kidneys, and analysed by reverse transcription-polymerase chain reaction for various genes implicated in angiogenesis and metastasis in RCC.


RESULTS
Thalidomide failed to inhibit the growth of xenograft tumours. The expression of angiogenic genes, e.g. vascular endothelial growth factor and fibroblast growth factor type 2 (FGF-2) within normal and tumour-affected kidney tissue was not reduced by thalidomide. Intratumoral transcription of beta3-integrin, a critical component of angiogenesis, was significantly increased in response to thalidomide treatment (P < 0.01). There was also a trend to increased expression of FGF-2 and tumour necrosis factor-alpha in thalidomide-treated tumours.


CONCLUSIONS
These findings suggest that RCC is capable of adapting to the inhibitory effects of thalidomide. The current uncertainty surrounding the action of thalidomide in vivo warrants caution about its use in humans. Further studies of thalidomide should be carried out in animal models, particularly to establish its safety and effectiveness as part of a combined therapeutic strategy.
Douglas
M L
ML
Department of Surgery, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
Reid
J L
JL
Hii
S I
SI
Jonsson
J R
JR
Nicol
D L
DL
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002292:Carcinoma, Renal Cell / Q000098:blood supply / Q000188:drug therapy*; D002455:Cell Division; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007680:Kidney Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013792:Thalidomide / Q000627:therapeutic use*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D020533:Angiogenesis Inhibitors; D013792:Thalidomide