In solid tumors such as hepatocellular carcinoma (HCC), hypoxia is one of the important mechanisms of cancer development that closely influences cancer development, survival, and metastasis. The development of treatments for cancer was temporarily revolutionized by immunotherapy but continues to be constrained by limited response rates and the resistance and high costs required for the development of new and innovative strategies. In particular, solid tumors, including HCC, a multi-vascular tumor type, are sensitive to hypoxia and generate many blood vessels for metastasis and development, making it difficult to treat HCC, not only with immunotherapy but also with drugs targeting blood vessels. Therefore, in order to develop a treatment strategy for hypoxic tumors, various mechanisms must be explored and analyzed to treat these impregnable solid tumors. To date, tumor growth mechanisms linked to hypoxia are known to be complex and coexist with various signal pathways, but recently, mechanisms related to the Hippo signal pathway are emerging. Interestingly, Hippo YAP/TAZ, which appear during early tumor and normal tumor growth, and YAP/TAZ, which appear during hypoxia, help tumor growth and proliferation in different directions. Peculiarly, YAP/TAZ, which have different phosphorylation directions in the hypoxic environment of tumors, are involved in cancer proliferation and metastasis in various carcinomas, including HCC. Analyzing the mechanisms that regulate the function and expression of YAP in addition to HIF in the complex hypoxic environment of tumors may lead to a variety of anti-cancer strategies and combining HIF and YAP/TAZ may develop the potential to change the landscape of cancer treatment.
在肝细胞癌（HCC）等实体瘤中，缺氧是影响癌症发生、生存与转移的重要机制之一。免疫疗法的出现曾短暂革新了癌症治疗领域，但其发展仍受限于有限的应答率、耐药性以及开发新型创新策略所需的高昂成本。特别是包括HCC在内的多血管型实体瘤对缺氧环境高度敏感，会生成大量血管以促进转移和发展，这使得HCC不仅对免疫疗法难以响应，对抗血管生成药物也表现出治疗抵抗。因此，为制定针对缺氧性肿瘤的治疗策略，必须深入探索和分析多种机制以攻克这类顽固的实体瘤。迄今为止，已知与缺氧相关的肿瘤生长机制具有复杂性，并与多种信号通路共存，而近期研究发现Hippo信号通路相关机制正逐渐凸显其重要性。值得注意的是，在早期肿瘤和正常肿瘤生长阶段出现的Hippo YAP/TAZ，与缺氧环境下出现的YAP/TAZ，分别通过不同方向促进肿瘤生长和增殖。特别的是，在肿瘤缺氧微环境中具有不同磷酸化方向的YAP/TAZ，在包括HCC在内的多种癌症的增殖和转移过程中发挥关键作用。在肿瘤复杂的缺氧环境中，除了研究HIF的调控机制外，深入分析YAP功能与表达的调控机制，可能催生多样化的抗癌策略。联合靶向HIF与YAP/TAZ的治疗方案，或将具备改变癌症治疗格局的潜力。
Regulation of Tumor Microenvironment through YAP/TAZ under Tumor Hypoxia
肿瘤(癌症)患者之家