Sebastian Jeising, Ann-Christin Nickel, Johanna Trübel, Jörg Felsberg, Daniel Picard, Gabriel Leprivier, Marietta Wolter, My Ky Huynh, Marlene B Olivera, Kerstin Kaulich, Lena Häberle, Irene Esposito, Gunnar W Klau, Julia Steinmann, Thomas Beez, Marion Rapp, Michael Sabel, Sascha Dietrich, Marc Remke, Jan F Cornelius, Guido Reifenberger, Nan Qin
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引用次数: 0
Abstract
Purpose: Brain metastases represent the most common intracranial tumors in adults and are associated with a poor prognosis. We used a personalized in vitro drug screening approach to characterize individual therapeutic vulnerabilities in brain metastases.
Methods: Short-term cultures of cancer cells isolated from brain metastasis patients were molecularly characterized using next-generation sequencing and functionally evaluated using high-throughput in vitro drug screening to characterize pharmacological treatment sensitivities.
Results: Next-generation sequencing identified matched genetic alterations in brain metastasis tissue samples and corresponding short-term cultures, suggesting that short-term cultures of brain metastases are suitable models for recapitulating the genetic profile of brain metastases that may determine their sensitivity to anti-cancer drugs. Employing a high-throughput in vitro drug screening platform, we successfully screened the cultures of five brain metastases for response to 267 anticancer compounds and related drug response to genetic data. Among others, we found that targeted treatment with JAK3, HER2, or FGFR3 inhibitors showed anti-cancer effects in individual brain metastasis cultures.
Conclusion: Our preclinical study provides a proof-of-concept for combining molecular profiling with in vitro drug screening for predictive evaluation of therapeutic vulnerabilities in brain metastasis patients. This approach could advance the use of patient-derived cancer cells in clinical practice and might eventually facilitate decision-making for personalized drug treatment.
期刊介绍:
The Journal of Neuro-Oncology is a multi-disciplinary journal encompassing basic, applied, and clinical investigations in all research areas as they relate to cancer and the central nervous system. It provides a single forum for communication among neurologists, neurosurgeons, radiotherapists, medical oncologists, neuropathologists, neurodiagnosticians, and laboratory-based oncologists conducting relevant research. The Journal of Neuro-Oncology does not seek to isolate the field, but rather to focus the efforts of many disciplines in one publication through a format which pulls together these diverse interests. More than any other field of oncology, cancer of the central nervous system requires multi-disciplinary approaches. To alleviate having to scan dozens of journals of cell biology, pathology, laboratory and clinical endeavours, JNO is a periodical in which current, high-quality, relevant research in all aspects of neuro-oncology may be found.