gms | German Medical Science

73. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Griechischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

29.05. - 01.06.2022, Köln

Establishment of cell culture models from intracerebral carcinoma metastases for personalised preclinical evaluation of novel therapeutic approaches

Etablierung von Zellkulturmodellen aus intracerebralen Metastasen zur personalisierten präklinischen Evaluation neuer Therapieansätze

Meeting Abstract

  • presenting/speaker Sebastian Jeising - Universitätsklinikum Düsseldorf, Medizinische Fakultät, Düsseldorf, Deutschland; Universitätsklinikum Düsseldorf, Klinik für Neurochirurgie, Düsseldorf, Deutschland
  • Julia Steinmann - Universitätsklinikum Düsseldorf, Klinik für Neurochirurgie, Düsseldorf, Deutschland
  • Jörg Felsberg - Universitätsklinikum Düsseldorf, Institut für Neuropathologie, Düsseldorf, Deutschland
  • Dennis Sohn - Universitätsklinikum Düsseldorf, Klinik für Strahlentherapie und Radioonkologie, Düsseldorf, Deutschland
  • Kerstin Kaulich - Universitätsklinikum Düsseldorf, Institut für Neuropathologie, Düsseldorf, Deutschland
  • Guido Reifenberger - Universitätsklinikum Düsseldorf, Institut für Neuropathologie, Düsseldorf, Deutschland
  • Daniel Hänggi - Universitätsklinikum Düsseldorf, Klinik für Neurochirurgie, Düsseldorf, Deutschland
  • Marion Rapp - Universitätsklinikum Düsseldorf, Klinik für Neurochirurgie, Düsseldorf, Deutschland
  • Michael Sabel - Universitätsklinikum Düsseldorf, Klinik für Neurochirurgie, Düsseldorf, Deutschland
  • Ann-Christin Nickel - Universitätsklinikum Düsseldorf, Klinik für Neurochirurgie, Düsseldorf, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 73. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Griechischen Gesellschaft für Neurochirurgie. Köln, 29.05.-01.06.2022. Düsseldorf: German Medical Science GMS Publishing House; 2022. DocP047

doi: 10.3205/22dgnc360, urn:nbn:de:0183-22dgnc3605

Veröffentlicht: 25. Mai 2022

© 2022 Jeising et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.


Gliederung

Text

Objective: Brain metastases (BM) are frequent and most commonly arise from carcinomas of the lung and breast. Treatment options include neurosurgical resection and radiosurgery, in particular in patients with solitary or singular BMs, as well as radiotherapy and pharmacological treatments including an increasing number of targeted therapies. Nevertheless, survival of BM patients is still limited and novel, more effective treatment options are needed. We established primary cell culture models from BM patients to facilitate personalized preclinical drug screening and to evaluate different therapeutic strategies including radiotherapy and Tumor Treating Fields (TTFields).

Methods: To date, five cell culture models have been established, including three models derived from non-small cell lung cancer (NSCLC) BMs (BM1-3), and one model each from breast cancer (BM4) and esophageal cancer BMs (BM5). In vitro therapeutic approaches included irradiation with 30 Gy, TTFields treatment with 200 kHz for 72 h, and pharmacological treatments with standard chemotherapeutic drugs or molecularly targeted agents. Cell survival following treatments was assessed by MTT or CellTiterGlo assays.

Results: Next generation sequencing (NGS) of the NSCLC BM tissues and corresponding cell cultures identified identical mutations, including druggable KRAS or RET alterations. In vitro treatment of a KRAS-mutant model (BM1) with the RAF-inhibitor naporafenib led to higher cell death compared to chemotherapy with cisplatin, paclitaxel or pemetrexed. Similarly, treatment of a RET-altered model (BM2) with the RET-inhibitor selpercatinib cased higher cell death compared to standard chemotherapy. In BM1, but not in BM2, cell survival decreased at 48 h after irradiation. TTFields treatment for 72 h reduced cell survival by 30% in BM1, 24% in BM2, 21.5% in BM3 and 47% in BM4, but did not impair viability in BM5.

Conclusion: We successfully established cell culture models from BMs of different cancer types and validated the mutation profiles in NSCLC BM models by NGS. Molecularly targeted therapy of the BM1 and BM2 models showed stronger reductions in cell survival as compared to standard cytotoxic chemotherapy. In vitro response to irradiation varied, while TTFields treatment reduced viability in 4/5 BM models. Our data support a role of BM cell models for personalized assessment of therapy response and preclinical evaluation of novel therapeutic strategies.