Preclinical models for translational sarcoma research.

PURPOSE OF REVIEW

Sarcoma is a basket term for mesenchymal tumors for which more than 75 genetically and histologically distinct subtypes are recognized. Therapeutic progress has largely been achieved with classical chemotherapeutic drugs that were tested in empirical clinical trials. However, outcome in metastatic patients remains poor and with few exceptions numerous trials have failed or only provided limited improvement in recent years.

RECENT FINDINGS

Given the genomic heterogeneity, preclinical model systems will be indispensable to identify new molecular targets and to prioritize drugs and drug combinations. Cell culture is still widely used in preclinical sarcoma research to identify potential novel therapeutic approaches and resistance mechanisms. New and improved techniques in genome-wide and proteome-wide screens enable a better characterization. In addition to cell line xenograft mouse models, patient-derived xenografts crucially broadened and improved preclinical studies using primary human samples. Finally, novel strategies for genome editing, like CRISPR/Cas and sleeping beauty transposon, lead to development of novel genetically engineered cell lines and mouse models.

SUMMARY

The present review gives a non-comprehensive overview on current model systems used in sarcoma research and discusses their translational relevance. Those include cell lines, subtype-specific patient-derived cell lines and xenografts as well as developments in genome editing and genetically engineered cell lines and mouse models.