Experimental Models for Studying HPV-Positive and HPV-Negative Penile Cancer: New Tools for An Old Disease

SIMPLE SUMMARY: Penile cancer is an uncommon and understudied malignancy that is most commonly diagnosed in developing countries. Therapeutic advances have been slow, in part due to the lack of in vitro and in vivo models for testing new drugs before performing clinical trials. Recently, this difficulty has been partly overcome and multiple new pre-clinical models were reported. These important developments will help develop new therapies for penile cancer patients. The present review summarizes and discusses the available data concerning the pre-clinical models of penile cancer and their uses. Comparisons are drawn between different models, allowing researchers to choose the most adequate setting for their experiments. The remaining gaps in this array of penile cancer models are also discussed, in particular the lack of models for studying metastatic disease and cell lines representing tumors associated with human papillomavirus. ABSTRACT: Penile cancer is an uncommon malignancy that occurs most frequently in developing countries. Two pathways for penile carcinogenesis are currently recognized: one driven by human papillomavirus (HPV) infection and another HPV-independent route, associated with chronic inflammation. Progress on the clinical management of this disease has been slow, partly due to the lack of preclinical models for translational research. However, exciting recent developments are changing this landscape, with new in vitro and in vivo models becoming available. These include mouse models for HPV(+) and HPV(−) penile cancer and multiple cell lines representing HPV(−) lesions. The present review addresses these new advances, summarizing available models, comparing their characteristics and potential uses and discussing areas that require further improvement. Recent breakthroughs achieved using these models are also discussed, particularly those developments pertaining to HPV-driven cancer. Two key aspects that still require improvement are the establishment of cell lines that can represent HPV(+) penile carcinomas and the development of mouse models to study metastatic disease. Overall, the growing array of in vitro and in vivo models for penile cancer provides new and useful tools for researchers in the field and is expected to accelerate pre-clinical research on this disease.