Toni Stephenson Lymphoma Center.
Judy and Bernard Briskin Center for Multiple Myeloma Research, Beckman Research Institute and Comprehensive Cancer Center, City of Hope National Medical Center, Duarte, California, USA.
Curr Opin Oncol. 2021 Sep 1;33(5):520-525. doi: 10.1097/CCO.0000000000000765.
In the article, we focus on the role of SUMOylation in tumorigenesis and cancer-related processes, including Epithelial-mesenchymal transition (EMT), metastasis, resistance to cancer therapies, and antitumor immunity. Clinical perspective on small ubiquitin-like modifier (SUMO) inhibitors will be discussed.
SUMOylation regulates multiple important biologic functions including gene transcription, DNA damage repair, cell cycle, and innate immunity. The SUMO pathway enzymes are usually elevated in various cancers and linked with cancer progression and poor clinical outcomes for patients. Recent studies have revealed the role of SUMOylation in EMT and metastasis through regulating E-Cadherin and Snail expression. Multiple studies demonstrate SUMOylation is involved with chemoresistance and hormone treatment resistance. Oncogene Myc and SUMOylation machinery regulation has been revealed in pancreatic cancer. SUMOylation is involved in regulating antitumor immune response through dendritic cells and T cells. A breakthrough has been made in targeting SUMOylation in cancer as first-in-class SUMO E1 inhibitor TAK-981 enters clinical trials.
SUMOylation plays an important role in tumor EMT, metastasis, therapy resistance, and antitumor immune response. Pharmaceutical inhibition of SUMOylation has become promising clinical therapy to improve the outcome of the existing chemo and immune therapies.
综述目的：本文重点介绍 SUMO 化在肿瘤发生和癌症相关过程中的作用，包括上皮间质转化（EMT）、转移、癌症治疗耐药以及抗肿瘤免疫。本文将讨论小泛素样修饰物（SUMO）抑制剂的临床观点。
最新发现：SUMO 化调节多种重要的生物学功能，包括基因转录、DNA 损伤修复、细胞周期和先天免疫。SUMO 通路中的酶在各种癌症中通常升高，并与癌症进展和患者的不良临床结局相关。最近的研究揭示了 SUMO 化通过调节 E-钙黏蛋白和 SNAIL 表达在 EMT 和转移中的作用。多项研究表明 SUMO 化参与化疗耐药和激素治疗耐药。致癌基因 Myc 和 SUMO 化机制的调节已在胰腺癌中得到揭示。SUMO 化通过调节树突状细胞和 T 细胞参与抗肿瘤免疫反应。作为首个靶向 SUMO 化的药物，TAK-981 已进入临床试验，这在癌症治疗方面取得了突破。
总结：SUMO 化在肿瘤 EMT、转移、治疗耐药和抗肿瘤免疫反应中发挥重要作用。抑制 SUMO 化已成为改善现有化疗和免疫治疗效果的有前途的临床治疗方法。
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