Ricci Francesca, Guffanti Federica, Affatato Roberta, Brunelli Laura, Roberta Pastorelli, Fruscio Robert, Perego Patrizia, Bani Maria Rosa, Chiorino Giovanna, Rinaldi Andrea, Bertoni Francesco, Fratelli Maddalena, Damia Giovanna
Laboratory of Molecular Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS Milan 20156, Italy.
Protein and Gene Biomarkers Unit, Laboratory of Mass Spectrometry, Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS Milan 20156, Italy.
Am J Cancer Res. 2020 Feb 1;10(2):572-580. eCollection 2020.
Mucinous ovarian carcinoma (mEOC) represents a rare subtype of epithelial ovarian cancer, accounting for 3-4% of all ovarian carcinomas. The rarity of this tumor type renders both the preclinical and clinical research compelling. Very few preclinical and models exist. We here report the molecular, metabolic and pharmacological characterization of two patient derived xenografts (PDXs) from mEOC, recently obtained in our laboratory. These PDXs maintain the histological and molecular characteristics of the patient's tumors they derived from, including a wild type . Gene expression analysis and metabolomics profile suggest that they differ from high grade serous/endometrioid ovarian carcinoma PDXs. The pharmacological characterization was undertaken testing the antitumor activity of both cytotoxic agents (cisplatin, paclitaxel, yondelis, oxaliplatin and 5-fluorouracile) and targeted agents (bevacizumab and lapatinib). These newly established mucinous PDXs do recapitulate mEOC and will be of value in the preclinical development of possible new therapeutic strategies for this tumor type.
黏液性卵巢癌（mEOC）是上皮性卵巢癌的一种罕见亚型，占所有卵巢癌的3%-4%。这种肿瘤类型的罕见性使得临床前和临床研究都很有吸引力。临床前模型非常少。我们在此报告了最近在我们实验室获得的两个源自mEOC患者的异种移植瘤（PDX）的分子、代谢和药理学特征。这些PDX保留了它们所源自的患者肿瘤的组织学和分子特征，包括野生型。基因表达分析和代谢组学谱表明它们与高级别浆液性/子宫内膜样卵巢癌PDX不同。进行了药理学特征分析，测试了细胞毒性药物（顺铂、紫杉醇、曲贝替定、奥沙利铂和5-氟尿嘧啶）和靶向药物（贝伐单抗和拉帕替尼）的抗肿瘤活性。这些新建立的黏液性PDX确实重现了mEOC，并且将在针对这种肿瘤类型的可能新治疗策略的临床前开发中具有价值。
