Preclinical Validation for Drug Repurposing in Thyroid Carcinoma

Drug repurposing is a relevant concept for many diseases, including cancer. Druggable targets could be identified using massive datasets in genetic sequencing, drug-target interactions, and meta-analyses. Ideally, drugs should be clinically feasible for the patient population, available in generic form and accessible within EU.

Currently, there is no cure for metastatic cancer, including Thyroid Carcinoma (TC). The solution is anticipated to be a fully personalized medicine approach using synergic combination therapies. Synergy is most likely achieved by combining approved targeted therapy, such as tyrosine kinase inhibitors (TKIs) with generic compounds at subtherapeutic doses. Importantly, genetic data from individual patient tumors should be sequenced using next generation sequencing (NGS) techniques to provide an ultimate personalized medicine platform.

A huge challenge is validating potential compounds from in silico to in vitro and ex vivo. The most convenient in vitro model for TC are commercially available cell lines. Advantages include familiar genetic characteristics and straightforward culture methods, making them suitable for drug screening. However, commercial cell lines do not fully represent individual patient characteristics, and drug screening results should be interpreted very cautious. A more suitable alternative are patient derived tumor cells (PDTCs). PDTCs are obtained from tumor material, dissociated to single cells, and subsequently cultured for a limited number of passages. This ex vivo culture system resembles individual tumor properties and drug sensitivities to a great extent, indicating a translational relevant system. Nonetheless, this platform is rather laborious since it requires optimal culture conditions, genetic validation of culture populations and logistic planning.

The current study aims to validate drug repurposing candidates using in vitro and ex vivo culture methods in TC to ultimately identify compounds that could offer remedy for metastatic TC patients. Identifying synergic compounds in commercial TC cell lines and establishment of PDTCs are topics that are tackled.