前列腺癌导管内癌（IDC-P）是2016年WHO新分类的前列腺癌病理类型，多与高肿瘤负荷、高侵袭性腺泡腺癌并存。合并IDC-P的患者病情进展快、预后极差且临床治疗方法极为有限。申请者前期首次报道了IDC-P对转移性前列腺癌和转移性去势抵抗性前列腺癌患者的预后影响，发现其对经典内分泌治疗存在天然耐药，却对新型内分泌治疗有效。目前，关于IDC-P的基础研究甚少，其发生、演进及耐药机制不明。为进一步解释这一现象及寻找新的治疗思路，本课题组前期通过显微切割、转录组测序、质谱分析等试验发现：IDC-P细胞可能通过MMP-10/LEF-1/CYP17A1-AKR1C3信号通路大量合成肿瘤内源性雄激素，最终导致其对经典内分泌治疗抵抗和肿瘤的恶性进展。通过证实该信号通路在IDC-P耐药和演进中的重要意义，可能为合并IDC-P的高侵袭性前列腺癌患者制订优化的治疗方案提供扎实的实验室依据。

Intraductal carcinoma of the prostate (IDC-P), a newly pathological entity in 2016 WHO classification, is frequently co-existing with high-tumor burden and aggressive classic acinar adenocarcinoma of prostate. Although patients with IDC-P often rapidly progress and associate with poor prognosis, there is still no efficient therapy available. Our study group have originally reported the unfavorable prognosis of IDC-P in mHSPC and mCRPC patients. We found that IDC-P seemed to be primary resistance to classical androgen deprivation therapy (ADT), however, with effective response to Abiraterone. To date, mechanism underlying ADT resistance, relapse and metastasis of IDC-P is limited and the exact molecular mechanism, unfortunately, is still unknown. In order to explain this special clinical phenomenon, various technical methods, including microdissection technology, RNA-sequence, LC/MS, qRT-PCR, Western bolt et al. have been used to explore the potential mechanism of ADT resistance and poor prognosis of patients with IDC-P. We found that the increased synthesis of intratumoral androgen initiated by a novel--MMP-10/LEF-1/CYP17A1-AKR1C3--signal pathway could be the basic reason. Based on these results mentioned above, we prospected to confirm this pivotal signaling axis in ADT resistance and rapid disease progression, and further illuminate the precise molecular mechanism with diverse methods and techniques. . MMP-10/LEF-1/CYP17A1-AKR1C3 signaling pathway would be expected to be one of the novel and promising targets in reversing relapse, metastasis and ADT resistance in patients with IDC-P.