PET/MR功能成像预测宫颈癌新辅助化疗敏感性及p53信号通路参与耐药机制的研究

新辅助化疗（NACT）可提高局部晚期宫颈癌可手术率及手术切除率，但NACT耐药会延误此类患者治疗时机。目前临床缺乏安全有效、可行性强的NACT疗效敏感性预测的影像学方法，而且对其耐药机制无统一定论。我们在前期基础研究中发现p53信号通路参与NACT起效机制，但是否参与耐药调控需要进一步研究。本研究综合运用一体机PET/MR多模态功能成像方法，包括葡萄糖（FDG）代谢显像、扩散加权成像（DWI）、灌注成像（PWI）及血氧水平依赖（BOLD）成像，同时获得宫颈癌NACT治疗前、后肿瘤在体状态下的多重功能成像信息指标，结合病理学指标，揭示宫颈癌NACT治疗敏感与耐药间病理生理差异机制；评价PET/MR功能成像预测宫颈癌NACT疗效敏感性的价值，获得相应的功能影像学定量指标；研究p53信号通路参与NACT耐药调控的证据和机制，为临床上宫颈癌克服药物抵抗治疗提供分子靶点和治疗依据。

Neoadjuvant chemotherapy (NACT) can improve operability and operative resective rate for locally advanced cervical cancer. However, drug resistance will delay effective therapy, which makes NACT a dilemma in clinics. Thus, to predict therapy sensitivity calls for a safe, effective and strongly feasible imaging method, and drug-resistance mechanisms for NACT are still under debate. In our previous laboratory study, p53 signaling pathway was identified to participate in NACT mechanisms, but evidence for their participation in regulating drug resistance needs further clarification. This study combines multi-modality functional imaging methods by hybrid PET/MR, including fluodeoxyglucose (FDG) metabolizing imaging, diffusion weighted imaging (DWI), perfusion weighted imaging (PWI) and blood oxygen level dependent (BOLD) imaging, as well as pathology indexes, to clarify the differences in pathophysiology between NACT drug sensitivity and drug resistance. Then we investigate the value of hybrid PET/MR functional imaging to predict response to NACT in cervical cancer and get according quantification indexes for functional imaging. Finally, we aim to find evidence for p53 signaling pathway to regulate NACT drug resistance, so as to provide some evidence in future molecular targeting therapy of cervical cancer by overcoming drug resistance.