Functional analysis of Sprouty-2 transcripts for determining the sensitivity to EGF-signaling inhibitors.

1、肿瘤细胞对吉非替尼的敏感性与Sprouty-2基因转录本的关系研究发现，人肺癌对易瑞沙(Gefitinib)的敏感性与Sprouty-2基因的两个转录本(分别为长和短)的表达模式有关。仅表达短形式Sprouty-2转录本的肿瘤对易瑞沙耐药，而表达长形式Sprouty-2转录本的肿瘤对易瑞沙敏感。Sprouty-2转录本可能是决定肿瘤对易瑞沙敏感性的新生物标志物。2)针对吉非替尼耐药肿瘤细胞的新策略1)MEK抑制剂和HDAC抑制剂的结合为ERK通路被结构性激活的肿瘤细胞的治疗提供了一种有效的化疗策略。2)PI3激酶/Akt通路抑制剂和阿霉素的联合为克服易瑞沙耐药的肿瘤细胞提供了一种有效的化疗策略。

1,Relationship between the sensitivity to Gefitinib and two Sprouty-2 transcripts in tumor cellsSensitivity to Iressa (gefitinib) in human lung cancers was found to be related with expression pattern of two transcripts of human Sprouty-2 genes (long and short forms, respectively). The tumors expressing only short forms of Sprouty-2 transcripts were resistant to Iressa, whereas the cells with long forms were sensitive. The Sprouty-2 transcripts may be a new biomarker for determining the sensitivity to Iressa in tumors.2,New strategies against Gefitinib (Iressa)-resistant tumor cells1)The combination of MEK inhibitors and HDAC inhibitors provides an efficient chemotherapeutic strategy for the treatment of tumor cells in which the ERK pathway is constitutively activated.2)The combination of a PI3 kinase/Akt pathway inhibitor and doxorubicin provides an efficient chemotherapeutic strategy for the treatment of tumor cells in which the PI3 kinase/Akt pathway is constitutively activated and the p53 pathway is functional.These combination therapies may be a new strategy for overcoming Iressa-resistance in tumors.