吉非替尼是目前临床上治疗非小细胞肺癌首选的靶向药物，但继发性耐药的产生是限制其疗效进一步提高的瓶颈。本课题组前期研究发现，药物转运体ABCC10对吉非替尼有高效转运功能，其表达及功能活性与非小细胞肺癌细胞株对吉非替尼的敏感性密切相关。本研究拟在前期工作基础上，从体外培养细胞模型、基因敲除及荷瘤动物模型、药物临床研究三个层次深入探索药物转运体ABCC10在吉非替尼获得性耐药中的作用，以及ABCC10基因多态性对吉非替尼药动学、药效学与不良反应的影响，有助于从多角度探索更全面的吉非替尼耐药机制与药物反应个体差异的产生机制，对于提高药物疗效、优化临床治疗方案及改善肿瘤患者生存预后具有重要意义。

Gefitinib is an orally active inhibitor of the epidermal growth factor receptor approved for use in patients with locally advanced or metastatic non-small cell lung cancer. However, acquired resistance to gefitinib after an initial good response remains a major obstacle to improving remission rates and achieving prolonged disease-free survival. Our previous studies suggested that the drug transporter ABCC10 could transport gefitinib effectively, and its expression level and functional activity closely related to the sensitivity to gefitinib in NSCLC cell lines. In this project, using NSCLC cell lines, knockout mice, mouse xenograft models, and NSCLC cancer patients, we will explore the role of ABCC10 in acquired resistance to gefitinib, and the influence of ABCC10 gene polymorphism on the pharmacokinetics, pharmacodynamics, and side effects of gefitinib. Our study will reveal a new and major factor that contributes to new preventive and therapeutic approaches to gefitinib resistance. It is of great importance to develop a new targeted therapy based on drug transporter to ensure drug safety, benefit future therapeutic interventions and improve the survival of cancer patients.