Guanylate cyclase C as a target for prevention, detection, and therapy in colorectal cancer.
Guanylate cyclase C as a target for prevention, detection, and therapy in colorectal cancer.
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DOI：
10.1080/17512433.2017.1292124
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发表时间：
2017-05
影响因子：
4.4
通讯作者：
Waldman SA
中科院分区：
文献类型：
--
作者：
Aka AA;Rappaport JA;Pattison AM;Sato T;Snook AE;Waldman SA
结直肠癌仍然是美国癌症死亡的第二大原因，需要新的策略来预防、检测和治疗该疾病。受体鸟苷酸环化酶 C (GUCY2C) 是一种由肠上皮表达的肿瘤抑制因子，已成为一个有前途的靶点。这篇综述概述了 GUCY2C 在肿瘤发生中的作用，以及将 GUCY2C 靶向方案转化为临床的步骤。内源性 GUCY2C 激活配体在肿瘤发生早期消失，使其信号轴沉默并实现转化。临床前模型支持 GUCY2C 配体补充作为一种新型疾病预防范例。随着 FDA 最近批准 GUCY2C 配体、利那洛肽和另外两种正在研发中的合成配体，该策略可以在人体试验中进行测试。除了初级肿瘤预防之外，我们还回顾了针对转移性病灶表达的 GUCY2C 的免疫疗法，以及使用 GUCY2C 作为检测和患者分期的生物标志物的平台。第一个针对患者的 GUCY2C 靶向方案的结果将在未来几年内公布。确定 GUCY2C 配体丢失是结直肠肿瘤发生的必要条件，有可能将治疗范式从不可逆的基因突变疾病转变为可治疗的配体不足疾病。
Colorectal cancer remains the second leading cause of cancer death in the United States, and new strategies to prevent, detect, and treat the disease are needed. The receptor, guanylate cyclase C (GUCY2C), a tumor suppressor expressed by the intestinal epithelium, has emerged as a promising target. This review outlines the role of GUCY2C in tumorigenesis, and steps to translate GUCY2C-targeting schemes to the clinic. Endogenous GUCY2C-activating ligands disappear early in tumorigenesis, silencing its signaling axis and enabling transformation. Pre-clinical models support GUCY2C ligand supplementation as a novel disease prevention paradigm. With the recent FDA approval of the GUCY2C ligand, linaclotide, and two more synthetic ligands in the pipeline, this strategy can be tested in human trials. In addition to primary tumor prevention, we also review immunotherapies targeting GUCY2C expressed by metastatic lesions, and platforms using GUCY2C as a biomarker for detection and patient staging. Results of the first GUCY2C targeting schemes in patients will become available in the coming years. The identification of GUCY2C ligand loss as a requirement for colorectal tumorigenesis has the potential to change the treatment paradigm from an irreversible disease of genetic mutation, to a treatable disease of ligand insufficiency.
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影响因子：
3.6
作者：
Brenna Ø;Furnes MW;Munkvold B;Kidd M;Sandvik AK;Gustafsson BI
通讯作者：
Gustafsson BI
影响因子：
120.7
作者：
Engels, Eric A.;Pfeiffer, Ruth M.;Fraumeni, Joseph F., Jr.;Kasiske, Bertram L.;Israni, Ajay K.;Snyder, Jon J.;Wolfe, Robert A.;Goodrich, Nathan P.;Bayakly, A. Rana;Clarke, Christina A.;Copeland, Glenn;Finch, Jack L.;Fleissner, Mary Lou;Goodman, Marc T.;Kahn, Amy;Koch, Lori;Lynch, Charles F.;Madeleine, Margaret M.;Pawlish, Karen;Rao, Chandrika;Williams, Melanie A.;Castenson, David;Curry, Michael;Parsons, Ruth;Fant, Gregory;Lin, Monica
通讯作者：
Lin, Monica
DOI：
10.1073/pnas.93.25.14827
发表时间：
1996-12-10
影响因子：
11.1
作者：
Carrithers, SL;Barber, MT;Waldman, SA
通讯作者：
Waldman, SA
影响因子：
9.8
作者：
Chey, William D.;Lembo, Anthony J.;Johnston, Jeffrey M.
通讯作者：
Johnston, Jeffrey M.
影响因子：
39.2
作者：
Friis, Soren;Riis, Anders H.;Sorensen, Henrik T.
通讯作者：
Sorensen, Henrik T.