Oncotarget：利用抗生素靶向杀灭癌症干细胞

  近日，来自曼彻斯特大学的研究人员Michael P. Lisanti在同其女儿进行交谈的过程中萌发出一个奇特的想法，是否可以利用传统抗生素的副作用来来清除癌症干细胞。文章中研究者研究了抗生素对癌症干细胞线粒体的作用，这或许为开启新型的抗癌疗法提供一定的帮助，相关研究发表于国际杂志Oncotarget上。

  我们都知道，线粒体是细胞的能量工厂，当然其同时也是癌症干细胞成熟分化成为肿瘤组织的能量来源；癌症干细胞和所有癌症的复发和癌症组织生长直接相关，其也是许多正常疗法治疗癌症的一个盲点。本文中，研究者表示，抗生素可以影响细胞的线粒体，那么其是否也会对癌症干细胞的线粒体产生明显的作用呢？

  随后研究者利用了5种不同类别的抗生素（其中一种为治疗粉刺的多西环素）对8种不同类型的肿瘤进行作用，在每一组测试中发现，其中四种抗生素都可以有效根除癌症干细胞，这8种肿瘤包括胶质母细胞瘤、肺癌、前列腺癌、乳腺癌、卵巢癌、胰腺癌及皮肤癌等；实验中抗生素对正常细胞并无有害影响，其都可以被批准可以用于人类机体的抗生素。

  本文研究为利用抗生素来治疗癌症开辟了先河，后期研究人员还需要进行更多的补充实验来证实这些抗生素杀灭癌细胞的效率。文章中当研究人员对肺癌患者进行实验时发现，阿奇霉素可以增加患者45%至75%的一年生存率，利用多西环素治疗淋巴瘤患者则可以完全消除疾病的症状，相关的研究结果表明，抗生素的抗癌特性实际上并不依赖于其抗感染的能力。

  最后研究者Federica Sotgia说道，这些抗生素相比当前的抗癌疗法非常便宜，其可以帮助有效改善癌症患者的生存质量及机体健康，我们有理由相信在下一个十年里我们将可以更为广泛地使用抗生素来作为抗癌疗法，给患者带来真正的价值。（转化医学网360zhyx.com）

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转化医学网推荐的原文摘要：

Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: Treating cancer like an infectious disease.
Oncotarget
Lamb R1, Ozsvari B1, Lisanti CL2, Tanowitz HB3, Howell A1, Martinez-Outschoorn UE4, Sotgia F1, Lisanti MP1.Here, we propose a new strategy for the treatment of early cancerous lesions and advanced metastatic disease, via the selective targeting of cancer stem cells (CSCs), a.k.a., tumor-initiating cells (TICs). We searched for a global phenotypic characteristic that was highly conserved among cancer stem cells, across multiple tumor types, to provide a mutation-independent approach to cancer therapy. This would allow us to target cancer stem cells, effectively treating cancer as a single disease of "stemness", independently of the tumor tissue type. Using this approach, we identified a conserved phenotypic weak point - a strict dependence on mitochondrial biogenesis for the clonal expansion and survival of cancer stem cells. Interestingly, several classes of FDA-approved antibiotics inhibit mitochondrial biogenesis as a known "side-effect", which could be harnessed instead as a "therapeutic effect". Based on this analysis, we now show that 4-to-5 different classes of FDA-approved drugs can be used to eradicate cancer stem cells, in 12 different cancer cell lines, across 8 different tumor types (breast, DCIS, ovarian, prostate, lung, pancreatic, melanoma, and glioblastoma (brain)). These five classes of mitochondrially-targeted antibiotics include: the erythromycins, the tetracyclines, the glycylcyclines, an anti-parasitic drug, and chloramphenicol. Functional data are presented for one antibiotic in each drug class: azithromycin, doxycycline, tigecycline, pyrvinium pamoate, as well as chloramphenicol, as proof-of-concept. Importantly, many of these drugs are non-toxic for normal cells, likely reducing the side effects of anti-cancer therapy. Thus, we now propose to treat cancer like an infectious disease, by repurposing FDA-approved antibiotics for anti-cancer therapy, across multiple tumor types. These drug classes should also be considered for prevention studies, specifically focused on the prevention of tumor recurrence and distant metastasis. Finally, recent clinical trials with doxycycline and azithromycin (intended to target cancer-associated infections, but not cancer cells) have already shown positive therapeutic effects in cancer patients, although their ability to eradicate cancer stem cells was not yet appreciated.