Bosutinib, dasatinib, imatinib, nilotinib, and ponatinib differentially affect the vascular molecular pathways and...

Area of Science:

• Pharmacology
• Oncology
• Vascular Biology

Background:

• Tyrosine kinase inhibitors (TKIs) are crucial in treating chronic myeloid leukemia (CML).
• Some TKIs (nilotinib, ponatinib, dasatinib) are linked to vascular adverse events (VAEs), but the mechanism remains unclear.
• A direct effect on vascular cells has been hypothesized.

Purpose of the Study:

• To investigate the impact of five TKIs (imatinib, nilotinib, dasatinib, bosutinib, ponatinib) on human vascular endothelial cells (HUVECs).
• To explore the effects on HUVEC function, including tube formation, cell viability, and gene expression.

Main Methods:

• Treatment of HUVECs with imatinib, nilotinib, dasatinib, bosutinib, and ponatinib.
• Assessment of HUVEC tube formation and cell viability.
• Analysis of gene expression profiles and molecular pathways.

Main Results:

• Distinct gene expression profiles were observed between dasatinib, nilotinib, ponatinib, and bosutinib, imatinib.
• Dasatinib, nilotinib, and ponatinib uniquely altered molecular pathways compared to other TKIs.
• Angiogenesis and HUVEC function (tube formation, viability) were negatively impacted by dasatinib, nilotinib, and ponatinib, but not imatinib or bosutinib.

Conclusions:

• The findings support a direct detrimental effect of certain TKIs on vascular cells.
• These results correlate with observed clinical differences in vascular adverse events (VAEs) among TKIs.
• This study provides a basis for further research into TKI-induced vascular toxicity.