CEDOC, Departamento de Imunologia, Faculdade de Ciências Médicas, FCM, Universidade Nova de Lisboa, Lisboa, Portugal.
A functional vascular endothelial growth factor A (VEGF-A) autocrine loop is crucial for bladder cancer cell survival. We reasoned that treatment with the anti-VEGF antibody bevacizumab may result either in cell growth prevention or in the cell adaptation to compensate VEGF deprivation.
The cytotoxicity of different levels of bevacizumab and its effect on the gene expression was analyzed in human bladder cancer cell lines.
Inhibition of bladder cancer cell proliferation was observed at >2.5 mg/ml of bevacizumab. Non-muscle-invasive bladder cancer cells expressed high concentrations of VEGF-A, and were less susceptible to bevacizumab inhibition. At 0.5 mg/ml (FDA approved concentration) of bevacizumab, cells increase their expression of VEGF-A, VEGF-A receptors and related growth factors.
Bevacizumab cytotoxicity is only observed at high concentration, and it is inversely correlated with the basal VEGF-A expression of the bladder cancer cells. This is the first report showing that, at clinical bevacizumab concentrations, cancer cells compensate the VEGF-A blockade, by improving the expression of VEGF-A and related genes, highlighting the need to follow the patient's adaptation response to bevacizumab treatment.
Videira PA, Piteira AR, Cabral MG, Martins C, Correia M, Severino P, Gouveia H, Carrascal M, Almeida JF, Trindade H, Santos LL. Are you the author?
Reference: Urol Int. 2011 Jan 8. Epub ahead of print.