Investigator, Assoc Prof (M)
Radiation Oncology,
Mass General Research Institute
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Associate Professor of Radiation Oncology
Harvard Medical School
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angiogenesis; hypoxia; metastasis; tumor biology
As part of the Edwin L. Steele Laboratory for Tumor Biology, the primary research focus at the Xu Laboratory is on the role and the molecular mechanism of tumor-host interaction in tumor angiogenesis and metastasis. The process of cancer metastasis consists of a long series of sequential, interrelated steps. The outcome of the process is dependent on both the intrinsic properties of the tumor cells and the responses of the host. Hypoxia and acidic pH are common features of solid tumors. Recently we discovered for the first time that tumor acidic microenvironment up-regulates the expression of an angiogenic factor, VEGF, via the ERK1/2 MAPK pathway. Subsequently, we showed that tumor hypoxia up-regulates another angiogenic factor, interleukin 8, via the PI3K/Akt pathway. One of the major obstacles to antiangiogenic therapy is that malignant tumors become resistant to treatments that target individual angiogenic factors by switching over to other angiogenic molecules. By using cDNA microarrays, we demonstrated that herceptin modulates the expression of multiple pro- and anti-angiogenic factors, leading to the normalization and regression of the vasculature in experimental human breast tumors. By using molecules like herceptin to target many angiogenic factors at once, we may improve the success rate of antiangiogenic therapy.
