Figure S1. The work flow of gene variation calling. (DOCX 195Â kb

Jing Gao (69330)

Jingyuan Wang (564061)

Lin Shen (507259)

Tiantian Tian (2735887)

Wanchun Zang (4848091)

Wenwen Huang (327269)

Yumei Lai (258213)

Zhentao Liu (3609254)

Zhi Jiang (269212)

Zhongwu Li (413576)

Zuhua Chen (4065085)

Journal of Hematology & Oncology

Figure S2. In vitro proliferation inhibitory activity of DiFi cells. (DOCX 18Â kb

The Francis Crick Institute

Additional file 4: of Characterization and validation of potential therapeutic targets based on the molecular signature of patient-derived xenografts in gastric cancer

Table S2. Affinity of BK011 and Erbitux (Cetuximab) for EGFR. (DOCX 13Â kb

Additional file 5: of Characterization and validation of potential therapeutic targets based on the molecular signature of patient-derived xenografts in gastric cancer

Table S1. The distribution of Q20 and Q30 representing quality control of sequencing. (DOCX 14Â kb

Additional file 1: of Characterization and validation of potential therapeutic targets based on the molecular signature of patient-derived xenografts in gastric cancer

Additional file 2: of Characterization and validation of potential therapeutic targets based on the molecular signature of patient-derived xenografts in gastric cancer

Supplementary method. The synthesis details of BK011. (DOCX 13Â kb

Additional file 3: of Characterization and validation of potential therapeutic targets based on the molecular signature of patient-derived xenografts in gastric cancer

Abstract Background Patient-derived xenograft (PDX) models with definite molecular signature are attractive preclinical models for development of novel targeted drugs. Here, we profiled and explored potential therapeutic targets based on characterized PDX models for advanced gastric cancer (AGC). Methods The genomic variation and molecular profile of 50 PDX models from AGC patients were analyzed by targeted next-generation sequencing, in situ hybridization, and immunohistochemistry. The antitumor activities of several targeted drugs were investigated in the PDX models. Furthermore, response biomarkers were explored. Results Each PDX model had individual histopathological and molecular features, and recurrent alterations in the MAPK, ErbB, VEGF, mTOR, and cell cycle signaling pathways were major events in these PDX models. Several potential drug targets, such as EGFR, MET, and CCNE1, were selected and validated in this study. Volitinib demonstrated strong antitumor activity in PDX models with MET and phosphorylated MET (pMET) overexpression. The EGFR monoclonal antibodies BK011 and cetuximab inhibited tumor growth in a PDX model with EGFR amplification. Afatinib inhibited tumor growth in the PDX models with EGFR amplification, EGFR overexpression, or HER2 amplification. Apatinib was more sensitive in the PDX models with high microvessel density. The CDK1/2/9 inhibitor AZD5438 had superior anti-tumor activity in two models with higher copy number of CCNE1. Conclusions PDX models with defined molecular signature are useful for preclinical studies with targeted drugs, and the results should be validated in larger studies with PDX models or in clinical trials

Zuhua Chen

Wenwen Huang

Tiantian Tian

Wanchun Zang

Jingyuan Wang

Zhentao Liu

Zhongwu Li

Yumei Lai

Zhi Jiang

Jing Gao

Lin Shen

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Characterization and validation of potential therapeutic targets based on the molecular signature of patient-derived xenografts in gastric cancer

https://figshare.com/articles/Additional_file_1_of_Characterization_and_validation_of_potential_therapeutic_targets_based_on_the_molecular_signature_of_patient-derived_xenografts_in_gastric_cancer/5881849

Additional file 2: of Characterization and validation of potential therapeutic targets based on the molecular signature of patient-derived xenografts in gastric cancer

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