Abstract 3850: Establishment of patient derived model of high-risk endometrial cancer for pre-clinical combined carboplatin and decitabine therapy

Abstract

Abstract Objective: The high risk endometrial cancers (EC), including high grade EC, serous carcinoma (SC), clear cell carcinoma (CC) and carcinosarcoma, account for 50% of death. Therapies for them are limited and patient derived tumor xenograft (PDX) model become useful tools to predict response to treatment. Here we compared the two methods of establishment of PDX models and evaluated the efficacy of carboplatin and decitabine in two high grade EC PDX models. Methods: Fresh tumor tissues collected from 11 primary high risk EC patients (6 high grade ECs, 4 SCs, 1 CC and 1 carcinosarcoma) were engrafted subcutaneously and in subrenal capsule in SCID mice. For those subcutaneous models, tumors were then orthotopic transplanted into uterine cavity. Histology, vimentin, cytokeratin, ER, PR, P53 expression were evaluated, together with mutation profiles by next generation sequencing for 500 cancer-panel genes. The efficacy of carboplatin and decitabine were evaluated in two high grade EC models. Results: The total tumor take rate was 81.8% (9 /11), without regard to engraft methods. The tumor take rate was higher in subrenal capsule models than subcutaneous models (70% vs 54.5%, respectively). The time for tumor formation (from transplantation to 1 cm in diameter) varies greatly from 4 weeks to 5 months. We observed good similarity between primary tumors and corresponding different passage of xenografts. One high grade EC model was sensitive to carboplatin and decitabine treatment whereas another was drug resistant. Two models harbor different genetic mutation profiles. Conclusion: The high tumor take rate ensures the establishment of the high risk EC biobank which provides a powerful resource for pre-clinical drug-sensitive tests as well as identification of biomarkers of response or resistance. Note: This abstract was not presented at the meeting. Citation Format: Weiwei Feng, Menghan Zhu, Yinhua Yu, Wei Jiang. Establishment of patient derived model of high-risk endometrial cancer for pre-clinical combined carboplatin and decitabine therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3850. doi:10.1158/1538-7445.AM2017-3850