Establishment and Characterization of Paclitaxel-Resistant Breast Cancer PDX Models

MAS98.12 PDX was established in-house and described previously (18 (link)). The paclitaxel resistant sub-line MAS98.12PR was established from a mouse bearing MAS98.12 tumor that was treated with 15 mg/kg paclitaxel twice per week for three weeks and after the initial response developed resistance as shown in Figure 1A. HBCx39 PDX was established at the Institute Curie (Paris, France) (19 (link), 20 (link)) and was obtained through collaboration with Dr. Elisabetta Marangoni. All xenografts were maintained by serial passaging, implanting 1-3 mm³ pieces of the parental tumors into thoracic mammary glands of 6-8 week-old female HSD : Athymic Nude Foxn1nu mice locally bred at the Department of Comparative Medicine at the Norwegian Radium Hospital (Oslo, Norway). Before implantation, the mice were placed under anesthesia with sevoflurane (Baxter, Deerfield, IL, USA).
The treatments were initiated when tumor volume reached 60-200 mm³ and lasted for three weeks. Paclitaxel (Hospira UK Ltd, Hurley, UK or Sandoz, Basel, Switzerland) diluted in 0.9% saline was given intravenously (i.v), while capecitabine (Accord-UK, Barnstaple, UK) diluted in 40 mM citric buffer/5% gummi arabicum and everolimus (LC Laboratories, Woburn, MA, US) diluted in 0.5% methyl cellulose solution were given orally. Tumor growth was followed by measuring their size (length L and width W) using a caliper, and the tumor volume was calculated as: W² x L x 0.5.
This study is compliant with all relevant ethical regulations regarding animal research and was conducted according to the recommendations of the European Laboratory Animals Science Association. All experiments involving animals were approved by the Norwegian Food Safety Authority (FOTS id 15499).