Influence of alectinib and crizotinib on ionizing radiation - in vitro analysis of ALK/ROS1-wildtype lung tissue cells

Jost T, Schultz AK, Frey B, Vu J, Fietkau R, Distel L, Hecht M (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Neoplasia Neoplasia

Book Volume: 27

Article Number: 100780

DOI: 10.1016/j.neo.2022.100780

Abstract

(1) Background: Just little is known about the interaction of ALK/ROS1-targeting kinase inhibitors with ionizing radiation (IR), particularly regarding side effects. We investigated the toxicity in two different lung cell lines both ALK/ROS1 wildtype (healthy and tumor origin) as representatives for normal lung tissue; (2) Methods: Human lung cell line BEAS-2B and malignant A549 lung cancer cells (ALK/ROS1 wt) were treated with alectinib or crizotinib, 2 Gy irradiation or a combination of KI and IR. Cell toxicity was analyzed by cell death (Annexin, 7AAD), colony forming, migration assay and live-cell imaging (TMRM, DRAQ7, Caspase3/7). Cell cycle (Hoechst) were analyzed by flow cytometry; (3) Results: Crizotinib led to higher cell death rates than alectinib, when cells were treated with 10 µM KI. Alectinib induced a more intense growth inhibition of colonies. Both inhibitors showed additive effects in combination with irradiation. Combination treatment (IR + KI) does not lead to synergistic effect on neither cell death nor colony forming; (4) Conclusions: The influence of simultaneous KI and IR was studied in non-mutated ALK/ROS1 cell lines. Both KIs seems to be well tolerated in combination with thoracic radiotherapy and lacked synergistic reinforcement in cellular toxicity. This supports the feasibility of ALK/ROS1 inhibition in combination with thoracic irradiation in future clinical trials.

Authors with CRIS profile

Tina Jost Department of Radiation Oncology Benjamin Frey Department of Radiation Oncology Rainer Fietkau Lehrstuhl für Strahlentherapie Luitpold Distel Department of Radiation Oncology Markus Hecht Department of Radiation Oncology

How to cite

APA:

Jost, T., Schultz, A.K., Frey, B., Vu, J., Fietkau, R., Distel, L., & Hecht, M. (2022). Influence of alectinib and crizotinib on ionizing radiation - in vitro analysis of ALK/ROS1-wildtype lung tissue cells. Neoplasia, 27. https://doi.org/10.1016/j.neo.2022.100780

MLA:

Jost, Tina, et al. "Influence of alectinib and crizotinib on ionizing radiation - in vitro analysis of ALK/ROS1-wildtype lung tissue cells." Neoplasia 27 (2022).

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