National Cancer Institute, National Institutes of Health, Mammary Biology & Tumorigenesis Laboratory, Bethesda, MD 20892, USA.
Expert Opin Ther Pat. 2010 Dec;20(12):1739-49. doi: 10.1517/13543776.2010.530659. Epub 2010 Nov 13.
Emerging evidence has clearly implicated an inappropriate activation of embryonic regulatory genes during cell transformation in adult tissues. An example of such a case is the embryonic gene Cripto-1. Cripto-1 is critical for embryonic development and is considered a marker of undifferentiated embryonic stem cells. Critpo-1 is expressed at low levels in adult tissues, but is re-expressed at a high frequency in a number of different types of human carcinomas, therefore, representing an attractive therapeutic target in cancer.
This review surveys different approaches that have been used to target Cripto-1 in cancer as reflected by the relevant patent literature as well as peer-reviewed publications. Potential involvement and targeting of Cripto-1 in neurodegenerative and degenerative muscle diseases are also discussed.
The reader will gain an overview of different mAbs, vaccines or oligonucleotides antisense targeting Cripto-1. A humanized anti-Cripto-1 antibody is currently being tested in a Phase I clinical trial in cancer patients.
Targeting Cripto-1 in human tumors has the potential to eliminate not only differentiated cancer cells but also destroy an undifferentiated subpopulation of cancer cells with stem-like characteristics that support tumor initiation and self-renewal.
新出现的证据清楚地表明，在成人组织中的细胞转化过程中，胚胎调节基因的激活是不合适的。这种情况的一个例子是胚胎基因 Cripto-1。Cripto-1 对胚胎发育至关重要，被认为是未分化胚胎干细胞的标志物。Cripto-1 在成人组织中的表达水平较低，但在许多不同类型的人类癌中高频重新表达，因此，它是癌症治疗的一个有吸引力的靶点。
本综述涵盖了不同的方法，这些方法被用于通过相关专利文献和同行评议出版物来靶向癌症中的 Cripto-1。还讨论了 Cripto-1 在神经退行性和退行性肌肉疾病中的潜在参与和靶向作用。
读者将获得对不同的单克隆抗体、疫苗或反义寡核苷酸靶向 Cripto-1 的概述。一种人源化抗 Cripto-1 抗体目前正在癌症患者的 I 期临床试验中进行测试。
靶向人类肿瘤中的 Cripto-1 不仅有可能消除分化的癌细胞，还有可能破坏具有支持肿瘤起始和自我更新特征的未分化癌细胞亚群。
