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Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis.
Cancer Cell. 2009 Mar 3; 15(3):220-31
Hong Zhao, Cornell Medical University, USA. F1000 Diabetes & Endocrinology
20 Apr 2010 | Changes Clinical Practice, Confirmation
Changes clinical practice - Singular anti-angiogenic agents should not be prescribed to cancer patients; instead anti-angiogenic drugs should routinely be used as part of combination therapy in order to impede the negative effects of anti-angiogenics, which may induce invasiveness of residual tumors.
This study provided significant evidence in animal studies to tell us that angiogenesis inhibitors in treating cancer are really a 'two-bladed sword': they can shrink tumors and improve survival, but, unfortunately, they can also drive tumor progression to more invasive phenotypes.
Anti-angiogenesis has been shown to be a successful strategy for tumor treatment. However, recent experimental evidence has been reported to show that, after a certain period of anti-angiogenesis treatment, the tumor in mouse models became more aggressive via compensative pathways. This study conducted by Marta Pàez-Ribes et al. further demonstrates that (in several animal models, e.g. RIP1-Tag2 model of pancreatic neuroendocrine cancer and glioblastoma multiform) (1) specific vascular endothelial growth factor receptor 2 (VEGFR2) inhibitors can increase the invasiveness of tumors; (2) the invasive phenotype is persistent after cessation of anti-VEGFR2 treatment; (3) tumors carrying a genetic deletion of the Vegf-A gene possess increased invasiveness; (4) hypoxia developed in the treated tumors concomitant with invasion. For additional background reading, please see refs {1-3}.
References: {1} Casanovas et al. Cancer Cell 2005, 8:299-309 [PMID:16226705]. {2} Du et al. Cancer Cell 2008, 13:206-20 [PMID:18328425]. {3} Blouw et al. Oncogene 2007, 26:4531-40 [PMID:17297464].
Competing interests: No potential interests relevant to this article were reported.
Zhao H: "This study provided significant evidence in animal studies to tell us that angiogenesis inhibitors in..." Evaluation of: [Pàez-Ribes M et al. Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell. 2009 Mar 3; 15(3):220-31; doi: 10.1016/j.ccr.2009.01.027]. Faculty of 1000, 20 Apr 2010. F1000.com/2941956#eval2612054
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Zhao H: 2010. F1000.com/2941956#eval2612054
Faculty of 1000 evaluations, dissents and comments for [Pàez-Ribes M et al. Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell. 2009 Mar 3; 15(3):220-31; doi: 10.1016/j.ccr.2009.01.027]. Faculty of 1000, 20 Apr 2010. F1000.com/2941956
Short form
Faculty of 1000: 2010. F1000.com/2941956
Multiple angiogenesis inhibitors have been therapeutically validated in preclinical cancer models, and several in clinical trials. Here we report that angiogenesis inhibitors targeting the VEGF pathway demonstrate antitumor effects in mouse models of pancreatic neuroendocrine carcinoma and glioblastoma but concomitantly elicit tumor adaptation and progression to stages of greater malignancy, with heightened invasiveness and in some cases increased lymphatic and distant metastasis. Increased invasiveness is also seen by genetic ablation of the Vegf-A gene in both models, substantiating the results of the pharmacological inhibitors. The realization that potent angiogenesis inhibition can alter the natural history of tumors by increasing invasion and metastasis warrants clinical investigation, as the prospect has important implications for the development of enduring antiangiogenic therapies.
DOI: 10.1016/j.ccr.2009.01.027
PMID: 19249680
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