通过核激素受体激活来抑制转移性黑色素瘤的广泛治疗
Nora Pencheva1, Colin G Buss1, Jessica Posada1
1Laboratory of Systems Cancer Biology, Rockefeller University, New York, NY 10065, USA.
Cell
|March 4, 2014
概括
用激素向肝X核激素受体 (LXR) 抑制黑色素瘤转移. 通过Apolipoprotein-E激活LXRβ,抑制瘤生长并提高存活率,提供了一个新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 药理学 药理学 是一个学科.
背景情况:
- 黑色素瘤转移仍然是一个重大的临床挑战,治疗选择有限.
- 肝X核激素受体 (LXR) 途径与各种细胞过程有关,但其在黑色素瘤中的作用尚未完全阐明.
研究的目的:
- 研究肝-X核激素受体 (LXR) 作为预防和治疗黑色素瘤转移的潜在治疗点.
- 阐明LXR对黑色素瘤进展和转移的影响背后的分子机制.
主要方法:
- 在黑色素瘤模型中使用LXR激活剂的药理管理.
- 包括基因表达和蛋白质分析在内的分子分析.
- 涉及LXRβ操纵的遗传研究.
- 在体内瘤生长,侵袭,血管生成和转移的评估.
- 对结合治疗与标准黑色素瘤治疗的评估.
主要成果:
- 口服LXR激动剂显著抑制了黑色素瘤的侵袭,血管新生,瘤的进展和转移.
- 确定了LXRβ激活是关键的调解者,诱导瘤和 stromal 细胞中的 apolipoprotein-E (ApoE).
- 通过LXRβ激动作用,在各种黑色素瘤突变背景和延长存活期中表现出有效性.
- 激活LXRβ与达卡巴,B-Raf抑制剂和抗CTLA-4抗体产生协同作用,克服了抗性.
结论:
- 肝X核激素受体 (LXR),特别是LXRβ,代表了黑色素瘤的可行的治疗标.
- 通过ApoE诱导激活LXRβ,有效抑制黑色素瘤转移和瘤生长.
- 向LXRβ提供了一个有前途的策略,有可能增强当前黑色素瘤疗法并克服耐药性.
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