„Yes, we (s)can“ : Molekulare Barcodes in der Tumorforschung für neue in vivo-Screening Verfahren
Dieser Beitrag erläutert die technologischen Fortschritte im Bereich des molekularen Zell-Barcodings. Dies, in Kombination mit quantitativen Hochdurchsatz-DNASequenzierungen und ausgefeilten Tiermodellen, lässt die Identifikation von klinisch relevanten Hemmstoffen der Metastasierung bei Krebserkrankungen näher rücken.
Although advances in the treat-ment and early detection of cancer have led to improvements in patient survival, cancer remains the second leading cause of deaths worldwide. The majority of cancer deaths are not caused by the primary tumor but by secondary metastases. The metastatic process is complex and still poorly understood on the molecular and cellular levels. The cancer cells need to leave the primary tumor, circulate through blood or lymph, extravasate at a secondary site and form micro-metastases that can eventually grow into macrometastases. The identifica-tion of clinically relevant inhibitors of metastasis is generally pursued by means of high-throughput drug screenings, which can only be tested in vitro. However, the underlying assays of these screenings do not adequately reflect the biological pro-cesses, which further complicates the search for clinically effective com-pounds and often causes the failure of potential drug candidates when trans-ferred into a clinical setting. On the other hand, studies in complex model systems in vivo are more adequate to reflect the complex interactions in the human body. Yet, those in vivo stud-ies are time, cost, and labour intensive and allow the study of very limited numbers of compounds only. To overcome these limitations, we devel-oped a multiplexed in vivo screen-ing platform that utilizes molecular DNA barcoding. In DNA barcoding technology, small random DNA sequences are incorporated into the DNA of cells to track them individu-ally in a pool of different cells. This technology allows quantification of multiple individual cell populations in parallel. With our platform we can simultaneously investigate hundreds of compounds regarding their effect on metastatic seeding in vivo with very low variability and high repro-ducibility. Using the multiplexed screening platform, we can not only identify novel potential candidates for a metastasis-specific therapy but also study and characterize the underlying cellular and molecular mechanisms.