Development of new gemcitabine that can overcome acquired gemicitabine resistancy

吉西他滨(吉西他滨)是迄今为止治疗胰腺癌患者的最佳化疗药物。然而，患者往往对GEM产生耐药性。为了克服这种获得性耐药，我们进行了分子分析，确定DCK是获得性耐药的关键分子；(1)获得性癌细胞中高频率的失活突变，(2)将DCK导入耐药细胞恢复对GEM的化疗敏感性，以及(3)在亲本细胞中敲除DCK获得耐药。这些结果表明，DCK的失活突变是获得GEM抗性的关键变化之一。

Gemcitabine (GEM here-in after) is the best chemotherapeutic agent to patients with pancreatic cancer to date. However, patients often acquire resistance to GEM. In order to overcome this acquired chemo-resistance, we performed molecular analyses and identified DCK as the key molecule for acquired resistance; (1) high frequency of inactivating mutation in acquired cancer cells, (2) introduction of DCK to resistant cells recovered chemo-sensitivity to GEM, and (3) knockdown of DCK in parental cells acquired chemo-resistance. These results demonstrate that inactivating mutation of DCK is one of the key alterations for acquisition of GEM resistance.