通过靶向自噬在侵袭前阶段攻克乳腺癌。
Attacking breast cancer at the preinvasion stage by targeting autophagy.
作者信息
Espina Virginia, Wysolmerski John, Edmiston Kirsten, Liotta Lance A
机构信息
George Mason University, Center for Applied Proteomics & Molecular Medicine, Manassas, VA 20110, USA.
出版信息
Womens Health (Lond). 2013 Mar;9(2):157-70. doi: 10.2217/whe.13.5.
Abstract
Preinvasive breast carcinoma cells that proliferate and accumulate within the nonvascular, closed intraductal niche are under severe hypoxic and metabolic stress. Understanding the survival mechanisms used by these cells has revealed therapeutic strategies for killing preinvasive neoplasms. We have found that autophagy ('self-eating') is a major survival strategy used by preinvasive carcinoma and breast cancer stem-like cells. Based on this finding, we have opened a clinical trial that is exploring neoadjuvant oral chloroquine antiautophagy therapy for ductal carcinoma in situ. We envision that antiautophagy therapy can be administered in combination with other treatments such as those that elevate intracellular calcium, to create a state of intolerable stress for preinvasive neoplastic cells, and thereby stop breast cancer before it starts.
摘要
在无血管的封闭导管微环境中增殖和积聚的乳腺原位癌细胞处于严重的缺氧和代谢应激状态。了解这些细胞所采用的生存机制已揭示出杀死原位肿瘤的治疗策略。我们发现自噬（“自我吞噬”）是原位癌和乳腺肿瘤干细胞所采用的主要生存策略。基于这一发现，我们开展了一项临床试验，探索新辅助口服氯喹抗自噬疗法治疗导管原位癌。我们设想抗自噬疗法可与其他治疗方法联合使用，比如那些能提高细胞内钙水平的方法，从而为原位肿瘤细胞创造一种无法耐受的应激状态，进而在乳腺癌起始之前将其阻止。
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