Patient-derived xenografts: a relevant preclinical model for drug development

Abstract

Identifying appropriate preclinical cancer models remains a major challenge in increasing the efficiency of drug development. A potential strategy to improve patient outcomes could be selecting the 'right' treatment in preclinical studies performed in patient-derived xenografts (PDXs) obtained by direct implants of surgically resected tumours in mice. These models maintain morphological similarities and recapitulate molecular profiling of the original tumours, thus representing a useful tool in evaluating anticancer drug response. In this review, we will present the state-of-art use of PDXs as a reliable strategy to predict clinical findings. The main advantages and limitations will also be discussed.

Keywords: Immunosuppressed mice; Orthotopic; Patient-derived-xenografts; Predictive value; Subcutaneous; Tumor heterogeneity.

Fig. 1

Figure show the take rate obtained by the implantation of tumor fragments from patients with colorectal cancer in different strains of immunodeficient mice. In particular, fragments from primary tumors of patient 128 (a) and of patient 130 (b) or from a metastatic limph node of patient 131 (c) were placed in medium supplemented with antibiotics, diced into 15–20 mm³ pieces, coated in Matrigel and implanted by a small incision and subcutaneous pocket made in one side of the lower back into different mice (F0). After tumor mass formation, at the indicated day, tumors were passaged (F1) and expanded in large cohorts for drug sensitivity experiments (F2). All animal procedures were approved by the ethics committee of the Regina Elena National Cancer Institute (CE/534/12) and were in compliance with the national and international directives (D.L. March 4, 2014, no. 26; directive 2010/63/EU of the European Parliament and of the council; Guide for the Care and Use of Laboratory Animals, United States National Research Council, 2011)

Fig. 2

NOD-SCID mice at passage F2 were treated with the G-quadruplex EMICORON per os at 15 mg/kg/day for 15 consecutive days, starting when a tumor volume of 300 mm³ was evident in mice. Each curve represent untreated (black) or EMICORON-treated mice (red)