Choi Sung Hoon, Kim Do Young
Institute of Health & Environment, Graduate School of Public Health, Seoul National University, Seoul 08826, Republic of Korea.
KoBioLabs Inc., Seoul 08826, Republic of Korea.
Cancers (Basel). 2024 Aug 30;16(17):3030. doi: 10.3390/cancers16173030.
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.
在肝癌（HCC）等实体瘤中，缺氧是癌症发展的重要机制之一，它密切影响癌症的发展、存活和转移。免疫疗法曾一度给癌症治疗带来了变革，但由于反应率有限、耐药性以及开发新的创新策略所需的高昂成本，其发展仍然受到限制。特别是包括HCC在内的实体瘤，这是一种多血管肿瘤类型，对缺氧敏感，并会生成许多用于转移和发展的血管，这使得治疗HCC变得困难，不仅免疫疗法难以奏效，针对血管的药物也难以发挥作用。因此，为了开发针对缺氧肿瘤的治疗策略，必须探索和分析各种机制，以治疗这些难以攻克的实体瘤。迄今为止，已知与缺氧相关的肿瘤生长机制很复杂，并且与各种信号通路共存，但最近，与Hippo信号通路相关的机制正在兴起。有趣的是，在肿瘤早期和正常肿瘤生长过程中出现的Hippo YAP/TAZ，以及在缺氧过程中出现的YAP/TAZ，在不同方向上促进肿瘤生长和增殖。特别的是，在肿瘤缺氧环境中具有不同磷酸化方向的YAP/TAZ，参与了包括HCC在内的各种癌症的增殖和转移。在肿瘤复杂的缺氧环境中，除了分析调节HIF外，还分析调节YAP功能和表达的机制，可能会带来多种抗癌策略，并且将HIF与YAP/TAZ相结合可能会开发出改变癌症治疗格局的潜力。
