A Review of Current Animal Models for the Study of Cervical Dysplasia and Cervical Carcinoma

Abstract

Cancer research has long relied on animal models for the study of disease mechanisms and new therapeutics. Future cancer treatments are likely to rely heavily on patient-derived xenograft models to develop novel treatments and tailor regimens to individual patient needs. However, specific models for cervical cancer and cervical dysplasia are limited. Only 3 models have been described in the published literature. A transgenic model for cervical cancer has allowed for the study of the differential contributions of the human papillomavirus 16 proteins E6 and E7 during oncogenesis. This model has also shown dysplasia development, although this has received little attention. A patient-derived tumor xenograft model where cervical cancer tissue is transplanted to the subcutaneous and orthotopic sites has been described. Here we review the reported transgenic and xenograft models, their strengths and limitations, and highlight the potential for the development of improved models to study cervical neoplasia.

A Suv39H1-low chromatin state drives migratory cell populations in cervical cancers

“…Following this, we sought to determine whether such Suv39H1 low populations are present in physiological settings, and if these putative populations show altered bulk chromatin organisation and features of enhanced migration. Current mouse models of cervical carcinogenesis do not sufficiently incorporate the physiology, variability, and patterns of metastatic spread observed in human cervical cancers 11 . To account for these aspects of cancer progression, we used a clinicopathological approach, combining histopathological analysis of human cervical biopsies with a meta-analysis of human cervical cancer data obtained from TCGA 12,13 .…”

A patient derived xenograft model of cervical cancer and cervical dysplasia

“…Further, it does not model human metastatic disease [ 6 ]. In addition, there are differences between the cellular mechanisms within cells that differ between mice and humans, for example telomerase activity in adult somatic cells[ 7 ]. The differences between human and mouse metabolism affect both tumour behaviour, and drug actions[ 8 ].…”

“…The difference between murine and human cancers has been observed in other tumour types [ 9 ] and hence xenograft models using tissue taken from human cancers have been developed. Immortalised cell lines frequently used in xenograft models have higher engraftment rates compared to primary cell lines but do not represent the full diversity of cell types within a tumour [ 7 ]. Unfortunately, the cell culture process irreversibly alters primary tumour cells from their natural phenotype [ 10 , 11 ].…”

Development of a goat model for evaluation of withaferin A: Cervical implants for the treatment of cervical intraepithelial neoplasia

“…There are several animal models utilized for the study of cervical pathologies with the majority being murine (Larmour et al, 2015). Testing a localized drug delivery approach for an investigational new drug using rodent models is not translatable to the clinical scenario due to size restrain of the rodent anatomy.…”