Systemic treatments for penile squamous cell carcinoma (pSCC) are toxic and inefficient. Patient-based preclinical models are essential to study novel treatments.
To establish a library of patient-derived tumor xenograft (PDX) models of human papillomavirus-positive (HPV+) and -negative (HPV-) pSCC and characterize these at the genomic and histological levels.
Eighteen tumor samples from 14 patients with recurrent or metastatic pSCC were implanted in nude mice. A biobank of PDX tumors was established after passaging of patient samples (F0) for three generations (F1, F2, F3) and was characterized using histopathology and targeted next-generation sequencing (tNGS). Single-nucleotide polymorphism fingerprinting was used to confirm PDX genealogy.
The engraftment rate, overall growth rate, and pSCC histomorphology were checked for each PDX generation. Staining for p40 (a pSCC marker) and p16 (a surrogate for HPV infection) was performed for F0 samples. The mutational profile according to a validated panel of 96 cancer genes was determined for F0 and F3 samples and compared to a larger tNGS database.
Including a previously established pilot model, 11 out of 18 tumor samples (61%) successfully engrafted in F1. The mean time from implantation in F1 to completion of F3 was 36 wk (standard deviation 18). Histological fidelity was demonstrated across generations. The patient mutational profiles were preserved in F3 and were representative of 277 pSCC samples in the Foundation Medicine database. The rapid progression of pSCC in patients from our selected high-risk cohort impeded the use of PDXs as avatars.
We successfully established the first library of 11 PDX models of HPV- and HPV+ pSCC. Our PDX models showed high engraftment rates and histological and genomic fidelity to the tumor tissue of origin. These models may help in paving the way towards the development of novel treatments.
We established 11 animal models based on tumor tissue from patients with penile cancer. These models could play a vital role in selection of novel treatments according to genetic mutations. In the future, therapies with confirmed preclinical effects may have a profound impact on the development of personalized treatments in penile cancer.
European urology focus. 2022 May 07 [Epub ahead of print]
Laura Elst, Anne-Sophie Van Rompuy, Eduard Roussel, Lien Spans, Isabelle Vanden Bempt, Andrea Necchi, Jeffrey Ross, Joseph M Jacob, Maria-Francesca Baietti, Eleonora Leucci, Maarten Albersen
Laboratory of Experimental Urology, Department of Development and Regeneration, KU Leuven, Leuven, Belgium; Department of Urology, University Hospitals Leuven, Leuven, Belgium., Department of Pathology, University Hospitals Leuven, Leuven, Belgium., Department of Human Genetics, University Hospitals Leuven, Leuven, Belgium., San Raffaele Hospital and Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Foundation Medicine, Cambridge, MA, USA; Upstate Medical University, Syracuse, NY, USA., Upstate Medical University, Syracuse, NY, USA., Trace, Department of Oncology, Leuven Cancer Institute, KU Leuven, Leuven, Belgium; Laboratory of RNA Cancer Biology, Department of Oncology, Leuven Cancer Institute, KU Leuven, Leuven, Belgium., Laboratory of Experimental Urology, Department of Development and Regeneration, KU Leuven, Leuven, Belgium; Department of Urology, University Hospitals Leuven, Leuven, Belgium. Electronic address: .