Establishment and genomic characterizations of patient-derived esophageal squamous cell carcinoma xenograft models using biopsies for treatment optimization

Abstract

BackgroundSquamous cell carcinoma is the dominant type of esophageal cancer in China with many patients initially diagnosed at advanced stage. Patient-derived xenografts (PDX) models have been developed to be an important platform for preclinical research. This study aims to establish and characterize PDX models using biopsy tissue from advanced esophageal cancer patients to lay the foundation of preclinical application.MethodsFresh endoscopic biopsy tissues were harvested from patients with advanced esophageal cancer and implanted subcutaneously into NOD/SCID mice. Then, the PDXs were serially passaged for up to four generations. Transplantation was analyzed and genomic characteristics of xenografts were profiled using next-generation sequencing.ResultsTwenty-five PDX models were established (13.3%, 25/188). The latency period was 75.12 ± 19.87 days (50–120 days) for the first passage and it decreased with increasing passaging. Other than tumor stages, no differences were found between transplantations of xenografts and patient characteristics, irrespective of chemotherapy. Histopathological features and chemosensitivity of PDXs were in great accordance with primary patient tumors. Each PDX was assessed for molecular characteristics including copy number variations, somatic mutations, and signaling pathway abnormalities and these were similar to patient results.ConclusionsOur PDX models were established from real time biopsies and molecularly profiled. They might be promising for drug development and individualized therapy.Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1379-9) contains supplementary material, which is available to authorized users.

A novel oral camptothecin analog, gimatecan, exhibits superior antitumor efficacy than irinotecan toward esophageal squamous cell carcinoma in vitro and in vivo

“…Tumor cell line xenografts were established by subcutaneous injection of 2 × 10 6 cells from in vitro cultures. Patient-derived xenograft (PDX) models were established in our lab according to previous studies 44 . Tumors were measured with fine calipers twice a week.…”

Targeted therapy of the AKT kinase inhibits esophageal squamous cell carcinoma growth in vitro and in vivo

“…Xanthohumol was reported to attenuate lung and breast cancer cell growth and the anticancer effects of xanthohumol were associated with the downregulation of EGFR, STAT3, Notch and nuclear factor‐κB (NF‐κB) . However, the mechanisms underlying its chemopreventive/therapeutic effects remain unresolved.…”

“…Xanthohumol was reported to attenuate lung and breast cancer cell growth and the anticancer effects of xanthohumol were associated with the downregulation of EGFR, STAT3, Notch and nuclear factor-κB (NF-κB). 21,41,42 However, the mechanisms underlying its chemopreventive/therapeutic effects remain unresolved. The present study focused on identifying a direct target of xanthohumol and we found that xanthohumol inhibited AKT kinase activity ( Figs.…”

“…Furthermore, the characteristics of drug responsiveness and mutational status also can be passed from generation to generation . Currently, PDX models are used to identify biomarkers and predict patient drug response in the clinic …”

“…[17][18][19] Currently, PDX models are used to identify biomarkers and predict patient drug response in the clinic. [20][21][22][23] Due to the multiple biological activities and relatively low systemic toxicity, natural anticancer products have gained attention from researchers. Xanthohumol is a prenylated flavonoid derived from the hop plant (Humulus lupulus L).…”