Niero Evandro Luís, Rocha-Sales Bianca, Lauand Camila, Cortez Beatriz Araujo, de Souza Marcelo Medina, Rezende-Teixeira Paula, Urabayashi Marcel Shiniti, Martens Adam Arai, Neves Jorge Henrique, Machado-Santelli Gláucia Maria
Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, Av, Prof, Lineu Prestes, 1524, Cidade Universitária, 05508-000 São Paulo, SP, Brazil.
J Exp Clin Cancer Res. 2014 Apr 28;33(1):37. doi: 10.1186/1756-9966-33-37.
Some cancers like melanoma and pancreatic and ovarian cancers, for example, commonly display resistance to chemotherapy, and this is the major obstacle to a better prognosis of patients. Frequently, literature presents studies in monolayer cell cultures, 3D cell cultures or in vivo studies, but rarely the same work compares results of drug resistance in different models. Several of these works are presented in this review and show that usually cells in 3D culture are more resistant to drugs than monolayer cultured cells due to different mechanisms. Searching for new strategies to sensitize different tumors to chemotherapy, many methods have been studied to understand the mechanisms whereby cancer cells acquire drug resistance. These methods have been strongly advanced along the years and therapies using different drugs have been increasingly proposed to induce cell death in resistant cells of different cancers. Recently, cancer stem cells (CSCs) have been extensively studied because they would be the only cells capable of sustaining tumorigenesis. It is believed that the resistance of CSCs to currently used chemotherapeutics is a major contributing factor in cancer recurrence and later metastasis development. This review aims to appraise the experimental progress in the study of acquired drug resistance of cancer cells in different models as well as to understand the role of CSCs as the major contributing factor in cancer recurrence and metastasis development, describing how CSCs can be identified and isolated.
例如,一些癌症,如黑色素瘤、胰腺癌和卵巢癌,通常对化疗表现出耐药性,这是患者预后改善的主要障碍。文献中经常呈现单层细胞培养、三维细胞培养或体内研究的成果,但很少有同一研究比较不同模型中耐药性的结果。本综述介绍了其中的几项研究,这些研究表明,由于不同的机制,三维培养的细胞通常比单层培养的细胞对药物更具耐药性。为了寻找使不同肿瘤对化疗敏感的新策略,人们研究了许多方法来了解癌细胞获得耐药性的机制。多年来,这些方法取得了很大进展,越来越多地提出使用不同药物的疗法来诱导不同癌症的耐药细胞死亡。最近,癌症干细胞(CSCs)受到了广泛研究,因为它们可能是唯一能够维持肿瘤发生的细胞。据信,癌症干细胞对目前使用的化疗药物的耐药性是癌症复发和后期转移发展的一个主要因素。本综述旨在评估不同模型中癌细胞获得性耐药性研究的实验进展,以及了解癌症干细胞作为癌症复发和转移发展的主要因素所起的作用,并描述如何识别和分离癌症干细胞。