Patient-Derived Xenograft (PDX) mouse models involve implanting human tumour tissues into immunodeficient mice, preserving the original tumour’s genetic and histological characteristics to closely mimic human cancer biology. Mouse Clinical Trials (MCTs) leverage these models in large, statistically powered cohorts to evaluate drug efficacy, predict clinical outcomes, and identify potential biomarkers, enhancing the translational relevance of preclinical oncology studies.

Oncology drugs generally have higher failure rates than other therapies, emphasising the need for better drug development. A major challenge is the lack of clinical efficacy despite promising preclinical results. Oncology drugs fail most in Phase II, where patient efficacy is first tested, which highlights the urgent need for more reliable preclinical models.

This gap may result from the type of model used and its accuracy. Traditional tumour models use immortalised cell lines grown in 2D and implanted in mice. These models help with early drug discovery, including pharmacology testing, by linking in vitro and in vivo data. However, growing tumour cells in 2D alters them, reducing their clinical relevance. Culturing heterogeneous tumour cells on plastic also favours uniform cell populations that no longer reflect the original tumour.

In contrast, PDX models are created by implanting patient tumours directly into immunocompromised mice without in vitro manipulation. Unlike cell line models, they avoid artificial selection pressures, making them more clinically relevant. PDX models are extensively characterised for pathology, growth, response to treatments, and genomic profiling using next-generation sequencing (NGS) technologies. Studies confirm that PDX models maintain the original tumour’s genomic integrity and closely match patient treatment responses.