Bevacizumab缺乏可靠的疗效预测指标，最近LDH却显示了潜在价值，机制不明！可能与以缺氧和有氧糖酵解为特征的肿瘤微环境相关。我们发现只有LDH升高的mCRC才有生存获益，且LDH与乏周细胞的血管数量相关，后者与bevacizumab敏感性相关；预试验提示LDH增加乳酸生成，乳酸促进血管内皮细胞迁徙和抑制周细胞迁徙，在缺氧状态下促进两者分泌TGF-β；肿瘤微环境中存在共生现象，共生关键分子MCT1与乏周细胞血管分布一致。本课题拟探讨微环境中LDH/乳酸以依赖HIF-1α方式通过 VEGFR-2促进内皮细胞生长、通过TGF-β受体抑制周细胞迁徙，从而生成大量乏周细胞的血管；敲除肿瘤微环境中的MCT1来阻断乳酸的利用，从而杀伤肿瘤和减少乏周细胞的血管生成；旨在阐明LDH预测bevacizumab疗效的机制，进而提出乏周细胞的血管是更加个体化的疗效预测指标以及MCT1是抗血管生成的新靶点！

No validated biomarker currently exists for bevacizumab. Recently LDH shows great potential for predict patients who can benefit from bevacizumab, although the mechanism remains elusive. We suspect that hypoxia and aerobic glycolysis in tumor microenvironment serve as the basis for the predict role of LDH. Our previous work shows that only patients who were with elevated LDH could get benefit from bevacizumab; and the vessels without pericyte coverage is related to LDH levels and the efficacy of bevacizumab; LDH increases lactate production, promotes invasion of endothelial cells while inhibits invasion of pericyte, and facilitates endothelial cell and pericyte secrete TGF-β under hypoxia condition; symbiosis exists in metastatic colorectal cancer and the distribution of MCT-1 is related with vessels without pericyte coverage. We plan to explore the mechanism by which the vessel without pericyte coverage generated, which might be results of lactate induced endothelial cells activation via VEGFR-2 and pericyte inhibition via TGF-β receptor, and both of them are in a HIF1α dependent pathway. What’s more, we plan to examine the impact of MCT-1 knockout on tumor grows and angiogenesis. By all of the above experiments, we aim to study the reason why LDH could predict the efficacy of bevacizumab, and evaluate whether vessel without pericyte coverage is with better predict value, as well as the therapeutic role of MCT-1.