英國一項最新研究顯示,，利用藥物改善惡性腫瘤中的血管狀況,，可以起到“軟化”腫瘤的作用，這有助于隨后實施放射療法殺死癌細胞,。
英國牛津大學(xué)3日發(fā)布新聞公報說,，一般來講，惡性腫瘤中的血管狀況不好,，會影響血液對癌細胞的供氧量,。該校研究人員通過動物實驗發(fā)現(xiàn)，通過藥物改善惡性腫瘤中的血管狀況,，可以增加腫瘤中的含氧量,，使得其對放射療法更為敏感，同時,，也有利于治療藥物被送達癌細胞,。
研究人員說，人們可能會以為改善腫瘤中的血管狀況會幫助癌細胞生長,，但實驗顯示這恰恰為放射療法做了“軟化”癌細胞的準(zhǔn)備,，從而能更有效地治療癌癥。
相關(guān)報告發(fā)表在新一期美國《癌癥研究》雜志上,。（生物谷Bioon.com）
生物谷推薦原始出處：
Cancer Research 69, 6347, August 1, 2009.doi: 10.1158/0008-5472.CAN-09-0657
Tumor Vascular Changes Mediated by Inhibition of Oncogenic Signaling
Naseer Qayum1, Ruth J. Muschel1, Jae Hong Im1, Lukxmi Balathasan1, Cameron J. Koch2, Sonal Patel3, W. Gillies McKenna1 and Eric J. Bernhard1
1 Gray Institute for Radiation Oncology and Biology, Oxford University, Oxford, United Kingdom; 2 Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania; and 3 PIramed Pharma, Slough, United Kingdom
Many inhibitors of the epidermal growth factor receptor (EGFR)-RAS-phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway are in clinical use or under development for cancer therapy. Here, we show that treatment of mice bearing human tumor xenografts with inhibitors that block EGFR, RAS, PI3K, or AKT resulted in prolonged and durable enhancement of tumor vascular flow, perfusion, and decreased tumor hypoxia. The vessels in the treated tumors had decreased tortuosity and increased internodal length accounting for the functional alterations. Inhibition of tumor growth cannot account for these results, as the drugs were given at doses that did not alter tumor growth. The tumor cell itself was an essential target, as HT1080 tumors that lack EGFR did not respond to an EGFR inhibitor but did respond with vascular alterations to RAS or PI3K inhibition. We extended these observations to spontaneously arising tumors in MMTV-neu mice. These tumors also responded to PI3K inhibition with decreased tumor hypoxia, increased vascular flow, and morphologic alterations of their vessels, including increased vascular maturity and acquisition of pericyte markers. These changes are similar to the vascular normalization that has been described after the antiangiogenic treatment of xenografts. One difficulty in the use of vascular normalization as a therapeutic strategy has been its limited duration. In contrast, blocking tumor cell RAS-PI3K-AKT signaling led to persistent vascular changes that might be incorporated into clinical strategies based on improvement of vascular flow or decreased hypoxia. These results indicate that vascular alterations must be considered as a consequence of signaling inhibition in cancer therapy.
