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LDL cholesterol counteracts the antitumour effect of tyrosine kinase inhibitors against renal cell carcinoma
Br J Cancer. 2017 Apr 25;116(9) :1203-1207
PMID: 28350788 PMCID: PMC5418451 URL: https://www.ncbi.nlm.nih.gov/pubmed/28350788
AbstractBACKGROUND: Treatment with tyrosine kinase inhibitors (TKIs) significantly improves survival of patients with renal cell carcinoma (RCC). However, about one-quarter of the RCC patients are primarily refractory to treatment with TKIs. METHODS: We examined viability of RCC and endothelial cells treated with low-density lipoprotein (LDL) and/or TKIs. Next, we validated the potential role of PI3K/AKT signalling in LDL-mediated TKI resistance. Finally, we examined the effect of a high-fat/high-cholesterol diet on the response of RCC xenograft tumours to sunitinib. RESULTS: The addition of LDL cholesterol increases activation of PI3K/AKT signalling and compromises the antitumour efficacy of TKIs against RCC and endothelial cells. Furthermore, RCC xenograft tumours resist TKIs in mice fed a high-fat/high-cholesterol diet. CONCLUSIONS: The ability of renal tumours to maintain their cholesterol homoeostasis may be a critical component of TKI resistance in RCC patients.British Journal of Cancer advance online publication, 28 March 2017; doi:10.1038/bjc.2017.77 www.bjcancer.com.
Notes1532-1827 Naito, Sei Makhov, Peter Astsaturov, Igor Golovine, Konstantin Tulin, Alexei Kutikov, Alexander Uzzo, Robert G Kolenko, Vladimir M Journal Article England Br J Cancer. 2017 Mar 28. doi: 10.1038/bjc.2017.77.