In:
International Journal of Cancer, Wiley, Vol. 147, No. 6 ( 2020-09-15), p. 1680-1693
Abstract:
What's new? Ponatinib is a small‐molecule multi‐tyrosine kinase inhibitor clinically approved for anticancer therapy. However, to date, the intracellular pharmacokinetics of this compound and the molecular mechanisms underlying resistance in cancer cells remain largely unknown. Here, the authors found that ponatinib was selectively scavenged by lipid droplets in cancer cells. Ponatinib accumulation into lipid droplets emerged as a critical determinant of intrinsic and acquired drug resistance. The findings suggest that lipid droplets represent an underestimated organelle influencing intracellular pharmacokinetics and anticancer tyrosine kinase inhibitor activity. Moreover, co‐targeting of lipogenic cancer cell phenotypes might enhance the efficacy of ponatinib and other lipophilic pharmaceuticals.
Type of Medium:
Online Resource
ISSN:
0020-7136
,
1097-0215
Language:
English
Publisher:
Wiley
Publication Date:
2020
detail.hit.zdb_id:
218257-9
detail.hit.zdb_id:
1474822-8
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