Guidance to rational use of pharmaceuticals in gallbladder sarcomatoid carcinoma using patient-derived cancer cells and whole exome sequencing

摘要: // Feiling Feng 1, * , Qingbao Cheng Liang Yang Dadong Zhang 2, 3 Shunlong Ji 2 Qiangzu Yihui Lin Fugen Li Lei Xiong Chen Liu 1 Xiaoqing Jiang Department of Biliary I, Third Affiliated Hospital PLA Second Military Medical University, Shanghai, China Division Translational Medicine, 3D Medicines Corporation, Changhai Hospital, The These authors have contributed equally to this work Correspondence to: Jiang, email: xqjiang_dandaoyike@163.com Liu, chliu_dandaoyike@163.com Xiong, simon.t@3dmedcare.com Keywords: gallbladder sarcomatoid carcinoma (GSC), patient-derived cancer cell (PDC), whole exome sequencing (WES), PIK3CA amplification, drug sensitivity Received: September 08, 2016      Accepted: November 22, Published: December 24, 2016 ABSTRACT Purpose: Gallbladder is a rare with no clinical standard treatment. With the rapid development next generation sequencing, it has been able provide reasonable treatment options for patients based on genetic variations. However, most drugs are not approval indications. correlation between response and variation needs be further elucidated. Experimental Design: Three cells-JXQ-3D-001, JXQ-3D-002, JXQ-3D-003, were derived from biopsy samples one patient progression characterized. In order study relationship gene alteration, mutations three cells discovered by screening performed alterations related signaling pathways that associated targets. Results: It found there differences in biological characteristics such as morphology, proliferation, migration colony formation activity among these although they same patient. Their sensitivities chemotherapy drugs-Fluorouracil, Doxorubicin, Cisplatin distinct. Moreover, none common could inhibit proliferations all cells. Comprehensive analysis their demonstrated tumor-associated genes TP53 AKT2 FGFR3 FGF10 SDHA PI3KCA mutated or amplified. Part actionable. By set compounds GDC-0941 PF-04691502 PI3K-AKT-mTOR pathway inhibitors dramatically decrease proliferation Importantly, expression phosphorylated AKT S6 markedly decreased after treatments (0.5 μM) (0.1 data suggested inhibition was activated amplification reduce proliferation. Conclusions: A model combined powerful tool elucidate alternations. cells, used biomarker indicate activation. Block may benefit alternation hypothesis. real efficacy confirmed vivo trial.