Fig. 1

Establishing a library of screenable in vitro and in vivo patient-specific squamous cell carcinoma (SCC) models for identification of therapeutic vulnerabilities. a Schematic representation of the pipeline for the generation of patient-personalized in vitro and in vivo models that can serve as a screening platform for uncovering therapeutic vulnerabilities. Resected tumours from human patients were grafted into NSG mice for the establishment of in vivo patient-derived xenograft (PDX) models, and for expansion of tumour material. Patient-derived primary culture (PDC) models were also derived and screened against small molecule libraries for identification of patient-specific therapeutics. Sections of patient tumours, as well as freeze-viable PDX and PDC models were stored in our biobank. Representative images of HN137-Pri and HN137-Met cultures are shown. b Hierarchical clustering of gene expression profiles for HN124, HN137 and HN148 paired primary (Pri) and metastatic (Met) PDXs in duplicates. Scale bar denotes Pearson’s correlation coefficient r from 0.8 (blue) to 1 (red). c Heat map of selected anti-cancer compounds exhibiting strong inhibition in at least one of the PDC lines. The scale represents percentage inhibition of the compounds, with inhibition score <50% shown in grey. d Selected molecular signatures (P < 0.05) of genes that show elevated expressions across the five Met cell lines, some of which appear to be associated with the selective responses of PDC lines to compounds of same target classes. e Six independent cohorts of mice (n = 6) bearing patient-matched PDX in one flank were treated with vehicle (control), 5 mg kg⁻¹ Flavopiridol (HN120), 40 mg kg⁻¹ Belinostat (HN148) and 8 mg kg⁻¹ Docetaxol (HN160). Scale bar, 1 cm. Error bars represent mean ± s.e.m. Two-tail Student’s t test was carried out between treatment and control groups on day 9 tumour weight. **P value <0.01 and ***P value <0.001