Dent Paul
Department of Neurosurgery; Massey Cancer Center; Virginia Commonwealth University; Richmond, VA USA.
Cancer Biol Ther. 2013 Sep;14(9):778-9. doi: 10.4161/cbt.26140. Epub 2013 Aug 15.
It has been known for many years that for a "normal" un-transformed cell to become immortal and subsequently tumorigenic requires multiple pro-oncogenic changes in the levels of protein expression and function. Genes most commonly associated with the process of oncogenesis include: p53 inactivating mutation; hDM2 overexpression; p16 reduced expression; K-/H-RAS activating mutation; PTEN inactivating mutation/deletion; EGFR activating mutation and overexpression; retinoblastoma inactivating mutation and deletion; Cyclin proteins overexpression; CD95 reduced expression; protective BCL-2 proteins overexpression; to name but just a few of such molecules.(1-5) That the minimally required specific proteins for oncogenesis are not known for many specific tumor types remains a challenge for the rational design of molecular targeted therapies.
多年来人们已经知道，一个“正常”的未转化细胞要变得永生化并随后具有致瘤性，需要蛋白质表达水平和功能发生多种促癌变化。最常与肿瘤发生过程相关的基因包括：p53失活突变；hDM2过表达；p16表达降低；K-/H-RAS激活突变；PTEN失活突变/缺失；EGFR激活突变和过表达；视网膜母细胞瘤失活突变和缺失；细胞周期蛋白过表达；CD95表达降低；保护性BCL-2蛋白过表达；仅列举其中一些此类分子。(1-5) 对于许多特定肿瘤类型而言，尚不明确肿瘤发生所需的最低限度特定蛋白质，这仍然是合理设计分子靶向疗法的一个挑战。
