Tumor heterogeneity and its implication for drug delivery.
Tumor heterogeneity and its implication for drug delivery.
复制标题
DOI：
10.1016/j.jconrel.2012.04.014
复制
发表时间：
2012-12-10
期刊：
影响因子：
--
通讯作者：
Bae YH
中科院分区：
文献类型：
--
作者：
Denison TA;Bae YH
越来越多的证据表明，患者肿瘤含有异质细胞群，每种细胞群对恶性肿瘤进展的程度和机制可能有所不同。然而，肿瘤药物递送研究领域虽然不断提出新的和创新的方法，但在许多方面仍然在基本上所有肿瘤细胞都是相同的前提下进行。在一些体内模型中，使用细胞系的异种移植肿瘤实际上可能是相对同质的，因此当据报道特定药物或递送系统成功治疗小鼠肿瘤时会产生过于令人鼓舞的结果。然而，众所周知，许多在临床前研究中显示成功的药物在临床试验中却会失败。肿瘤异质性可能是大多数治疗方法未能充分解决的最重要因素之一。虽然某种药物可能会取得初步成功，但在许多情况下，肿瘤生长的最终复发是由于细胞亚群不受药物机制影响、拥有或获得更大的耐药性，或者微环境中的局部状况使它们能够逃避或耐受药物。这些不同的亚群可能包括癌症干细胞、突变的克隆变体和肿瘤相关基质细胞，以及经历空间不同条件（例如扩散限制的肿瘤区域内缺氧）的细胞。这篇综述简要讨论了肿瘤异质性的许多方面及其对未来药物设计和递送方法的潜在影响。
Evidence continues to accumulate that patient tumors contain heterogeneous cell populations, each of which may contribute differently in extent and mechanism to the progression of malignancy. However, the field of tumor drug delivery research, while continually presenting new and innovative approaches, in many ways continues to operate on the premise that essentially all tumor cells are identical. In some in vivo models, xenograft tumors using cell lines may actually be comparatively homogeneous, and thus result in overly encouraging results when a particular drug or delivery system is reported to successfully treat tumors in mice. It is well known, however, that many drugs that show success in preclinical studies will fail in clinical trials. Tumor heterogeneity is possibly one of the most significant factors that most treatment methods fail to address sufficiently. While a particular drug may exhibit initial success, the eventual relapse of tumor growth is due in many cases to subpopulations of cells that are either not affected by the drug mechanism, possess or acquire a greater drug resistance, or have a localized condition in their microenvironment that enables them to evade or withstand the drug. These various subpopulations may include cancer stem cells, mutated clonal variants, and tumor-associated stromal cells, as well as cells experiencing a spatially different condition such as hypoxia within a diffusion-limited tumor region. This review briefly discusses some of the many aspects of tumor heterogeneity and their potential implications for future drug design and delivery methods.
登录
查看更多内容
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
2.5
作者：
Kim Y;Lin Q;Glazer PM;Yun Z
通讯作者：
Yun Z
影响因子：
11.2
作者：
Charafe-Jauffret E;Ginestier C;Iovino F;Wicinski J;Cervera N;Finetti P;Hur MH;Diebel ME;Monville F;Dutcher J;Brown M;Viens P;Xerri L;Bertucci F;Stassi G;Dontu G;Birnbaum D;Wicha MS
通讯作者：
Wicha MS
影响因子：
17.1
作者：
Liu J;Lau SK;Varma VA;Moffitt RA;Caldwell M;Liu T;Young AN;Petros JA;Osunkoya AO;Krogstad T;Leyland-Jones B;Wang MD;Nie S
通讯作者：
Nie S
影响因子：
5.3
作者：
Micke, P;Östman, A
通讯作者：
Östman, A