以系統化方法辨識出能用於標靶藥物輸送的癌症專一性細胞膜受體

Abstract

癌症是世界上主要死亡原因之一，目前已研發出相當多種類的抗癌藥作為治療手段。但是傳統的抗癌藥無法準確輸送到癌症患處，身體上其他正常的組織會因為抗癌藥的毒性而受到傷害。抗癌藥的副作用既會影響病人的生活品質，也降低了治療效果，故本研究的目標即為如何將抗癌藥準確送至癌細胞。現在的新方法是可將抗癌藥包裹在免疫微脂體中(immuno-liposome)，免疫微脂體表面的特定抗體會因為抗體-抗原親和力(antigen-antibody affinity)的反應而與癌細胞表面的目標蛋白質結合，達到抗癌藥對癌細胞的專一性輸送，然後抗癌藥會經由內吞作用進入癌細胞內。我們以一系統化的方法來分析去氧核醣核酸微陣列(DNA microarray)資料，以期能找出癌症專一性細胞膜受體(cancer-specific membrane receptor, CSMR)作為藥物輸送的目標。我們比較了癌症專一性細胞膜受體在癌症組織與在人體正常組織的mRNA表現量，希望能找出在癌症組織中為高表現、在大部分正常組織中為低表現的癌症專一性細胞膜受體。除此之外，我們也比較了癌症專一性細胞膜受體於數種癌症細胞株中的表現量。若癌症專一性細胞膜受體在某癌症細胞株中的表現量與在同類癌症組織中的表現量相似，該癌症細胞株則建議可用作實驗證明。

Cancer is a leading cause of death worldwide. Lots of anti-cancer drugs have been invented for cancer therapeutics. Traditional anti-cancer drugs with serious cytotoxicity would cause injuries of normal tissues owing to the incorrect drug delivery. The side-effects of anti-cancer drugs would not only debase the life quality of patients but decrease the therapeutic efficacy. The purpose of this study is to find a way to accurately deliver anti-cancer drugs to cancer cells. Currently, anti-cancer drugs encapsulated in the immunoliposome would be specifically transported to cancer cells by the mechanism of antigen-antibody affinity between the coated antibody of immunoliposome and its target protein on the surface of cancer cell and then enter the cancer cell by endocytosis. We propose a systematic method to identify cancer-specific membrane receptors (CSMRs) as the delivery target by analyzing DNA microarray data. We also compare the expression level of each CSMR in cancer tissue to that in normal tissues of body, and expect to identify the CSMR with high expression level in cancer but generally low expression level in all normal tissues. Besides, we compare the expression level of each CSMR in several cancer cell-lines. If the CSMR expression levels of cancer cell-lines are similar to that in the same type of cancer tissue, the CSMR is recommended for experimental verification.