Zebrafish Patient-Derived Xenografts Identify Chemo-Response in Pancreatic Ductal Adenocarcinoma Patients.
Alice UsaiGregorio di FrancoMargherita PiccardiPerla CateniLuca Emanuele PollinaCaterina VivaldiEnrico VasileNiccola FunelMatteo PalmeriLuciana DenteAlfredo FalconeDimitri GiunchiAlessandro MassoloVittoria RaffaLuca MorelliPublished in: Cancers (2021)
It is increasingly evident the necessity of new predictive tools for the treatment of pancreatic ductal adenocarcinoma in a personalized manner. We present a co-clinical trial testing the predictiveness of zPDX (zebrafish patient-derived xenograft) for assessing if patients could benefit from a therapeutic strategy (ClinicalTrials.gov: XenoZ, NCT03668418). zPDX are generated xenografting tumor tissues in zebrafish embryos. zPDX were exposed to chemotherapy regimens commonly used. We considered a zPDX a responder (R) when a decrease ≥50% in the relative tumor area was reported; otherwise, we considered them a non-responder (NR). Patients were classified as Responder if their own zPDX was classified as an R for the chemotherapy scheme she/he received an adjuvant treatment; otherwise, we considered them a Non-Responder. We compared the cancer recurrence rate at 1 year after surgery and the disease-free survival (DFS) of patients of both groups. We reported a statistically significant higher recurrence rate in the Non-Responder group: 66.7% vs. 14.3% (p = 0.036), anticipating relapse/no relapse within 1 year after surgery in 12/16 patients. The mean DFS was longer in the R-group than the NR-group, even if not statistically significant: 19.2 months vs. 12.7 months, (p = 0.123). The proposed strategy could potentially improve preclinical evaluation of treatment modalities and may enable prospective therapeutic selection in everyday clinical practice.
Keyphrases
- end stage renal disease
- ejection fraction
- clinical trial
- newly diagnosed
- free survival
- chronic kidney disease
- peritoneal dialysis
- prognostic factors
- gene expression
- squamous cell carcinoma
- radiation therapy
- mesenchymal stem cells
- patient reported outcomes
- study protocol
- papillary thyroid
- combination therapy
- rectal cancer