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Naito S, Makhov P, Astsaturov I, Golovine K, Tulin A, Kutikov A, Uzzo RG, Kolenko VM
LDL cholesterol counteracts the antitumour effect of tyrosine kinase inhibitors against renal cell carcinoma
Br J Cancer (2017) 116:1203-1207.
Abstract
BACKGROUND: 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.
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Publication Date: 2017-04-25.
PMCID: PMC5418451
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