Mouse models of thyroid cancer: A 2015 update

Abstract

Thyroid cancer is the most common endocrine neoplasm, and its rate is rising at an alarming pace. Thus, there is a compelling need to develop in vivo models which will not only enable the confirmation of the oncogenic potential of driver genes, but also point the way towards the development of new therapeutics. Over the past 20 years, techniques for the generation of mouse models of human diseases have progressed substantially, accompanied by parallel advances in the genetics and genomics of human tumors. This convergence has enabled the development of mouse lines carrying mutations in the genes that cause thyroid cancers of all subtypes, including differentiated papillary and follicular thyroid cancers, poorly differentiated/anaplastic cancers, and medullary thyroid cancers. In this review, we will discuss the state of the art of mouse modeling of thyroid cancer, with the eventual goal of providing insight into tumor biology and treatment.

Structural alterations in tumor‐draining lymph nodes before papillary thyroid carcinoma metastasis

“…The lack of successful treatment options for advanced thyroid cancer underscores the need for novel therapeutic strategies, as well as in vivo models that can help predict their clinical utility. In the past, in vivo models were developed by injecting human thyroid cancer cell lines into immunodeficient mouse strains . Immunodeficient models, however, fail to mimic the natural tumor microenvironment, because they do not evoke protective immune responses or tumor‐promoting inflammation .…”

“…Immunodeficient models, however, fail to mimic the natural tumor microenvironment, because they do not evoke protective immune responses or tumor‐promoting inflammation . For this reason, genetically engineered strains have been developed to study tumors that arise in situ in immunocompetent hosts . In order to rapidly induce tumor development, orthotopic injection of tumor cell lines derived from genetically engineered mice have also been used .…”

Immune responses in the thyroid cancer microenvironment: making immunotherapy a possible mission

“…In this study, 44% of patients receiving a therapeutic dose of virus experienced 24:12 a reduction in tumor size. Preclinical studies to support more human trials would benefit from exploring OVs in orthotopic, immunocompetent murine models of thyroid cancer (Vanden Borre et al 2014, Kirschner et al 2016.…”

Animal models of medullary thyroid cancer: state of the art and view to the future

“…These models were generated by overexpressing mutated oncogenic RET or other oncogenes in transgenic mice or through the loss of tumour suppressor genes (Cote et al 2015, Kirschner et al 2016, Wiedemann & Pellegata 2016.…”

“…Loss or mutations of these genes have been reported in many types of human cancers. It was found that mice bearing a single Rb mutant allele (Rb +/− ) develop pituitary tumours with almost complete penetrance (Cote et al 2015, Kirschner et al 2016. Rb +/− mice were also predisposed to develop C-cell hyperplasia, which subsequently progressed into MTC.…”