Xenografts derived from patients with head and neck cancer recapitulate patient tumour properties

Abstract

Rodent models mimic the heterogeneity of head and neck cancer (HNC) malignancies and are used to investigate HNC-associated biomarkers and evaluate drug responses. To assess the utility of patient-derived xenografts (PDXs) as an HNC model, 18 tumour samples were obtained from surgical specimens of patients with HNC and implanted into non-obese diabetic severe combined immunodeficient mice. The histological features of PDXs and corresponding patient samples were compared. Furthermore, the present study investigated how PDX responses to anticancer drugs mimic patient clinical responses, as well as the expression of adenosine triphosphate-binding cassette transporters through chemotherapy in an HNC-PDX model. A total of five PDXs from patients with HNC exhibiting high correspondence with histopathological features of the original patient samples were established (establishment rate, 28%). The responses of three PDXs to cisplatin were associated with clinical responses of the patients. ABC transporter expression was augmented in one PDX model after anticancer drug treatment, but not in PBS-treated passaged PDXs. PDX models exhibited similar biological and chemosensitive characteristics to those of the primary tumours. PDXs could be a useful preclinical tool to test novel therapeutic agents and identify novel targets and biomarkers in HNC.

Urokinase-Type Plasminogen Activator Receptor (uPAR) Expression and [64Cu]Cu-DOTA-AE105 uPAR-PET/CT in Patient-Derived Xenograft Models of Oral Squamous Cell Carcinoma

“…Our findings regarding the histological stability of PDX tumor tissue through passages are consistent with previous studies, in which it has been demonstrated that histological properties, biomarker expression, and mutational profile are stable through passages [35,[38][39][40]. Therapeutic response to anti-cancer therapy in PDX models has also been shown to resemble the clinical response in matched patients [35,40]. However, it has also been demonstrated that the human stromal composition is only maintained for early passages, after which the murine stroma dominates, suggesting that early passages may be better at resembling the donor tumor [41].…”

“…Especially, when exploring targets like uPAR, which is expressed on tumor-associated activated stromal cells. Our findings regarding the histological stability of PDX tumor tissue through passages are consistent with previous studies, in which it has been demonstrated that histological properties, biomarker expression, and mutational profile are stable through passages [35,[38][39][40]. Therapeutic response to anti-cancer therapy in PDX models has also been shown to resemble the clinical response in matched patients [35,40].…”