Cao Zhiyun, Weygant Nathaniel, Chandrakesan Parthasarathy, Houchen Courtney W, Peng Jun, Qu Dongfeng
Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.
Fujian Key Laboratory of Integrative Medicine in Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.
Cancers (Basel). 2020 Dec 17;12(12):3801. doi: 10.3390/cancers12123801.
Microtubule-associated doublecortin-like kinase 1 (DCLK1) is an accepted marker of tuft cells (TCs) and several kinds of cancer stem cells (CSCs), and emerging evidence suggests that DCLK1-positive TCs participate in the initiation and formation of inflammation-associated cancer. DCLK1-expressing CSCs regulate multiple biological processes in cancer, promote resistance to therapy, and are associated with metastasis. In solid tumor cancers, tumor epithelia, immune cells, cancer-associated fibroblasts, endothelial cells and blood vessels, extracellular matrix, and hypoxia all support a CSC phenotype characterized by drug resistance, recurrence, and metastasis. Recently, studies have shown that DCLK1-positive CSCs are associated with epithelial-mesenchymal transition, angiogenesis, and immune checkpoint. Emerging data concerning targeting DCLK1 with small molecular inhibitors, monoclonal antibodies, and chimeric antigen receptor T-cells shows promising effects on inhibiting tumor growth and regulating the tumor immune microenvironment. Overall, DCLK1 is reaching maturity as an anti-cancer target and therapies directed against it may have potential against CSCs directly, in remodeling the tumor microenvironment, and as immunotherapies.
微管相关双皮质素样激酶1（DCLK1）是公认的簇状细胞（TCs）和几种癌症干细胞（CSCs）的标志物，新出现的证据表明，DCLK1阳性的TCs参与炎症相关癌症的起始和形成。表达DCLK1的CSCs调节癌症中的多种生物学过程，促进对治疗的抗性，并与转移相关。在实体肿瘤癌症中，肿瘤上皮细胞、免疫细胞、癌症相关成纤维细胞、内皮细胞和血管、细胞外基质以及缺氧均支持具有耐药性、复发性和转移性特征的CSC表型。最近，研究表明，DCLK1阳性的CSCs与上皮-间质转化、血管生成和免疫检查点相关。有关用小分子抑制剂、单克隆抗体和嵌合抗原受体T细胞靶向DCLK1的新数据显示，在抑制肿瘤生长和调节肿瘤免疫微环境方面具有有前景的效果。总体而言，DCLK1作为抗癌靶点正逐渐成熟，针对它的疗法可能直接对CSCs具有潜力，在重塑肿瘤微环境方面以及作为免疫疗法方面均有潜力。
