Size Does Matter: Why Polyploid Tumor Cells are Critical Drug Targets in the War on Cancer.
Size Does Matter: Why Polyploid Tumor Cells are Critical Drug Targets in the War on Cancer.
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DOI：
10.3389/fonc.2014.00123
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发表时间：
2014
影响因子：
4.7
通讯作者：
Harding A
中科院分区：
文献类型：
--
作者：
Coward J;Harding A
肿瘤的演变是一个巨大的障碍，目前阻碍了真正治愈癌症的治疗方法的发展。从这个角度来看，我们主张这样一种假设，即基因组含量显著升高的肿瘤细胞（多倍体肿瘤细胞）促进了多种不可治愈癌症的快速肿瘤演变和治疗耐药性的获得。我们呼吁在酵母，癌症模型和癌症患者中进行的研究，这些研究都集中在多倍体能够实现大的表型飞跃的假设上，提供了许多不同的耐药表型。我们开发了一种基于流式细胞术的方法，用于定量多倍体肿瘤细胞的患病率，并显示这些细胞在患者肿瘤中的频率可能高于通常所理解的。然后，我们介绍了最近的研究，确定有前途的新的治疗策略，可用于特异性靶向癌症患者的多倍体肿瘤细胞。我们认为，这些治疗方法应纳入新的治疗策略，旨在通过杀死高度进化的，耐药的多倍体细胞亚群来阻断肿瘤的演变，从而帮助维持患者肿瘤的药物敏感状态。
Tumor evolution presents a formidable obstacle that currently prevents the development of truly curative treatments for cancer. In this perspective, we advocate for the hypothesis that tumor cells with significantly elevated genomic content (polyploid tumor cells) facilitate rapid tumor evolution and the acquisition of therapy resistance in multiple incurable cancers. We appeal to studies conducted in yeast, cancer models, and cancer patients, which all converge on the hypothesis that polyploidy enables large phenotypic leaps, providing access to many different therapy-resistant phenotypes. We develop a flow-cytometry based method for quantifying the prevalence of polyploid tumor cells, and show the frequency of these cells in patient tumors may be higher than is generally appreciated. We then present recent studies identifying promising new therapeutic strategies that could be used to specifically target polyploid tumor cells in cancer patients. We argue that these therapeutic approaches should be incorporated into new treatment strategies aimed at blocking tumor evolution by killing the highly evolvable, therapy-resistant polyploid cell subpopulations, thus helping to maintain patient tumors in a drug sensitive state.