Tissue cultures from patient derived xenografts (PDX): a new fast method to test the effect of therapeutic agents

PATACCINI G; VANZULLI S; LIGUORI M; ROJAS P; ELIA A; MARTÍNEZ VAZQUEZ P; BURRUCHAGA J; GONZALEZ P; GASS H; LANARI C; SEQUEIRA G

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Precision medicine needs to be accompanied by diagnostic toolsto determine which patient may benefit from therapeutic agents. Forthis purpose, to test drug efficacy, patient derived xenografts (PDX)or ex vivo assays are currently being developed. We have recentlyshown a 32% of success evaluating the effects of antiprogestins intissue cultures (BCTC). However, with this technique few treatmentscan be simultaneously tested due to the small size of breast cancersamples. The main aim of this study is to develop PDX from luminalbreast cancers and evaluate if BCTC from these PDX reproducethe observed drug effects. In this study, we evaluated the effect ofdoxorubicin (Dox; 1 μM) and/or paclitaxel (Pax; 50 nM) on 16 BCTC.In addition, 20 PDX were attempted inoculating breast cancer cellsinto NSG female mice treated or not with estrogen pellets (0.5 mg).The study was approved by institutional review boards. In the BCTCexposed to chemotherapeutic agents we observed histological andcytological changes related to Dox or Pax exposure such as macronuclei,necrotic foci and apoptosis. Most of the PDX developedsmall tumors and remained quiescent. PDX-485 started to growsimilarly in E2-treated or untreated mice. Tumor 485 was a tumorrelapse (luminal B; ER: 40%, PR: 30%, Ki-67 90%, HER2: negative).Dox inhibited tumor growth (p