Afatinib is active in osteosarcoma in osteosarcoma cell lines

Purpose Osteosarcoma is the most common bone tumor, mainly affecting adolescents and young adults, and metastatic disease has poor outcomes with a dismal overall survival. Currently, chemotherapy is the standard of care with limited results, finding that new therapies could improve these outcomes. P...

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Bibliographic Details
Published in:Journal of cancer research and clinical oncology 2020-07, Vol.146 (7), p.1693-1700
Main Authors: Cruz-Ramos, Marlid, Zamudio-Cuevas, Yessica, Medina-Luna, Daniel, Martínez-Flores, Karina, Martínez-Nava, Gabriela, Fernández-Torres, Javier, López-Reyes, Alberto, Solca, Flavio
Format: Article
Language:English
Subjects:
Antitumor activity
Bone cancer
Bone tumors
Cancer Research
Cell migration
Cell viability
Chemotherapy
ErbB protein
Etiology
Hematology
Internal Medicine
Kinases
Medicine
Medicine & Public Health
Metastases
Motility
Oncology
Original Article – Cancer Research
Osteosarcoma
Phosphorylation
Sarcoma
Signal transduction
Wound healing
Young adults
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Summary:Purpose Osteosarcoma is the most common bone tumor, mainly affecting adolescents and young adults, and metastatic disease has poor outcomes with a dismal overall survival. Currently, chemotherapy is the standard of care with limited results, finding that new therapies could improve these outcomes. Preclinical and clinical studies have suggested a possible important role of ErbB pathway aberrations in osteosarcoma etiology. The present study shows the effect of afatinib, an irreversible ErbB family blocker in osteosarcoma cell lines. Methods Within a panel of human osteosarcoma cell lines, we addressed cell viability assay using afatinib at increasing concentrations. Motility was measured in wound-healing assays and invasion capacity was assessed in Transwell chamber assays. Finally, to monitor ErbB pathway modulation by afatinib and related compounds, we used Western blot analyses. Results Cell viability inhibition, as well as a reduction of motility and migration of osteosarcoma cell line were observed after treatment with afatinib. Likewise, in the HOS cell line, afatinib decreased phosphorylation of key components in the ErbB signaling pathway. Conclusions Afatinib shows relevant antitumor effect in several osteosarcoma cell lines, as it causes a significant impact on cell viability, motility, and migration with a significant decrease in the activation of ErbB pathway activity.
ISSN:0171-5216
1432-1335
DOI:10.1007/s00432-020-03220-y