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.

Highlights

  • Ever since the first studies reported on the use of in vivo murine leukemia models for drug efficacy in the 1950s [1], vast efforts have been devoted to the development of animal models in cancer to predict the response of chemotherapeutics in humans

  • Patient-derived xenografts (PDXs), where tumour fragments from patients are directly implanted in immunodeficient mice and passed in vivo directly from mouse to mouse, have emerged as important tools for translational research

  • Our observations seem to confirm this hypothesis as demonstrated in patient-derived xenografts (PDXs) originating from one colorectal cancer patient and treated with a G-quadruplex (G4) ligand, one mouse showed complete response, two mice partial response followed by a rapid disease progression and no-response was elicited in one mouse (Fig. 2)

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Summary

Background

Ever since the first studies reported on the use of in vivo murine leukemia models for drug efficacy in the 1950s [1], vast efforts have been devoted to the development of animal models in cancer to predict the response of chemotherapeutics in humans. The introduction of a variety of immuno-deficient mice enabled us to engraft tumour cell lines by ectopic or orthotopic injection While this approach allows many models to be established with relative ease, these xenografts bear little resemblance with the original tumours, in terms of molecular complexity and tumour heterogeneity. Following the implantation of tumour fragments from NOD-SCID in nude mice (F1), tumours initially appeared but a subsequent regression was observed in 3 out 5 mice (Fig. 1b) On the contrary, both NOD-SCID and SCID mice seemed to represent a suitable model for the engraftment of colon cancer PDXs, as we a CRC-128

CD1 nude No tumor appearance
Findings
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