Renal cell carcinoma may adapt to and overcome anti-angiogenic intervention with thalidomide.

Abstract:

OBJECTIVE:To report on the failure of thalidomide to inhibit tumour growth in an animal model of human renal cell carcinoma (RCC). MATERIALS AND 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.

journal_name

BJU Int

journal_title

BJU international

authors

Douglas ML,Reid JL,Hii SI,Jonsson JR,Nicol DL

doi

10.1046/j.1464-410x.2002.02666.x

keywords:

subject

Has Abstract

pub_date

2002-04-01 00:00:00

pages

591-5

issue

6

eissn

1464-4096

issn

1464-410X

pii

2666

journal_volume

89

pub_type

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