Combining Molecular Profiling and Drug Screening for BM

Brain metastases (BM), the most common intracranial tumors in adults, are linked to poor prognosis in brain cancer.

Sebastian Jeising and the team aimed to use personalized in vitro drug screening to identify therapeutic vulnerabilities in patients with BM.

Short-term cultures of cancer cells from patients with BM were characterized using next-generation sequencing and high-throughput in vitro drug screening to identify pharmacological treatment sensitivities.

The results showed that next-generation sequencing identified matching genetic alterations in BM tissue samples and corresponding short-term cultures, indicating that these cultures are suitable models for replicating the genetic profile of BM and their drug sensitivity.

Using a high-throughput in vitro drug screening platform, researchers screened cultures from 5 BM for responses to 267 anticancer compounds, correlating drug responses with genetic data. Targeted treatments with JAK3, HER2, or FGFR3 inhibitors demonstrated anti-cancer effects in individual BM cultures.

The study concluded that combining molecular profiling with in vitro drug screening provides a proof-of-concept for predicting therapeutic vulnerabilities in patients with BM. This approach could enhance the use of patient-derived cancer cells in clinical practice and eventually aid in personalized drug treatment decision-making.

This research was funded by the German Childhood Cancer Foundation, the Research Commission of the Medical Faculty, Heinrich Heine University Düsseldorf.

Source: https://link.springer.com/article/10.1007/s11060-024-04763-7

Jeising, S., Nickel, AC., Trübel, J. et al. (2024). “A clinically compatible in vitro drug-screening platform identifies therapeutic vulnerabilities in primary cultures of brain metastases.” J Neurooncol (2024). https://doi.org/10.1007/s11060-024-04763-7.