Abstract 5061: Establishment of a comprehensive patient derived xenograft (PDX) collection for use in precision medicine; A project from START Madrid- FJD
Authors: Baños Natalia , Hernandez-Guerrero Tatiana , Bonilla Victoria , Doger Bernard , Del Puerto Laura , Robb Emily , Cadena Cecilio , Garcia-Foncillas Jesus , Moreno Victor , Wick Michael 
Published: September 2020

Background: Patient-derived xenografts (PDX) as xenotransplantation of human tumors into athymic nude mice have become the hallmark of preclinical modelling in cancer research. They are particularly useful in the characterization of targeted therapies in drug development. We sough to build a collection of PDX connected to our early phase trials facility for preclinical testing of new drugs.

Methods: Between March 2017 and October 2019, a total of 483 samples from patients with cancer were obtained for implant. A full review of the characteristics including histological particularities, molecular findings and treatment experience was reviewed for a full description of the collection.

Results: 483 tumor samples were implanted. A total of 157 achieved tumor growth (defined as a target volume of 150 mm3 in at least three consecutive measurements). Here, we present the description of 121 successfully engrafted models passed at least 2 times from initial implant. Most common type of cancer is colorectal adenocarcinoma (CRC=63; 52%) (MSI-H=8, 13%). 20 are molecularly characterized: KRAS: 9 (45%); NRAS=1 (5%) and BRAF=4 (20%). Prior therapy: chemo=16, VEGFi=9, EGFRi=1, ICi=1. Fifteen ovarian carcinomas (12,39%). Three BRCA2m (2) and EPCAMm (1). Eight breast carcinomas (6,6%): 6 Invasive Ductal Carcinomas (IDC) (three are triple negative with BRCA2m; 3 resistant to aromatase inhibitors, and 1 to a CDK inhibitor), 1 papillary carcinoma and 1 medullary carcinoma harboring a TP53 mutation. Eleven non-small cell lung cancers grew successfully, all EGFRwt (KRASm=2). One squamous cell carcinoma with a BRD4/NUTM1 fusion treated with cisplatin/vinorelbine and atezolizumab prior to implant. Eight glioblastomas (prior temozolomide=3 (37%), MGMTmt=5 (62%) and IDHm=1 (12%). One uveal melanoma with a MET fusion. The collection also includes endometrial MSI-H cancers (2), bladder (2), head and neck (1), kidney (4), pancreas (2), biliary tract (1) and cervix carcinomas (1) and one osteosarcoma.

Conclusions: The importance of PDX development programs relies on the reproducibility of tumors with specific oncogenic drivers potentially targetable. A full comprehensive characterization of PDX shareable collections are paramount for tracking of molecular, diagnostic, prognostic and predictive markers of drug response.

Citation Format: Natalia Baños, Tatiana Hernandez-Guerrero, Victoria Bonilla, Bernard Doger, Laura Del Puerto, Emily Robb, Cecilio Cadena, Jesus Garcia-Foncillas, Victor Moreno, Michael Wick. Establishment of a comprehensive patient derived xenograft (PDX) collection for use in precision medicine; A project from START Madrid- FJD [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5061.