Evidence Showing That Tumors Can Grow Without Angiogenesis and Can Switch Between Angiogenic and Nonangiogenic Phenotypes
Menée à l'aide d'un modèle murin de carcinome hépatocellulaire, cette étude met en évidence des mécanismes par lesquels, en "co-optant" un réseau vasculaire existant suite à un traitement anti-angiogénique (sorafénib), les tumeurs acquièrent une résistance thérapeutique
Although sorafenib is approved for the treatment of hepatocellular carcinoma (HCC), the ability of this anti-angiogenic tyrosine kinase inhibitor to extend survival in HCC patients is limited because of acquired drug resistance, whose mechanism is poorly understood. In this issue of the Journal, Kuczynski and colleagues (1) report a mechanism of acquired resistance to sorafenib using an orthotopic HCC xenograft model. The authors tell us how, although these HCC are initially angiogenic and respond to sorafenib, resistance occurs because the neoplastic cells switch to a non-angiogenic phenotype and actively co-opt the normal liver vasculature instead of inducing angiogenesis. These results have important implications for understanding this particular form of resistance to anti-angiogenic drugs and the biology of the tumors that can develop such a resistance. The non-angiogenic growth of tumors has already been hypothesized to be one of the possible reasons for intrinsic and/or acquired cancer resistance to anti-angiogenic treatment (2). In this paper, it is now proven that an angiogenic malignancy can, following treatment with a drug inhibiting sprouting angiogenesis, switch to a non-angiogenic phenotype in order to keep growing. This finding further supports the notion that neoplasia is not necessarily angiogenesis dependent as some tumors can be completely …