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Mechanisms of acquired tumor drug resistance
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer ( IF 9.7 ) Pub Date : 2019-08-20 , DOI: 10.1016/j.bbcan.2019.188310
Svetlana N. Aleksakhina , Aniruddh Kashyap , Evgeny N. Imyanitov

Systemic therapy often results in the reduction of tumor size but rarely succeeds in eradicating all cancer cells. Drug efflux, persistence of cancer stem cells (CSCs), epithelial-mesenchymal transition (EMT) and down-regulation of apoptosis are the most known general causes of therapy failure. Tumor escape from targeted compounds often involves pathway-specific mechanisms, which result in the restoration of the affected signaling cascade. The acquisition of drug resistance is mediated by mutations, changes in gene expression, alternative splicing, post-translational protein modifications, etc. Development of resistance to therapy may not necessary involve the emergence of new tumor clones: multiple studies demonstrate that even chemonaive neoplasms already have a small population of cells, which are capable of surviving therapeutic pressure and facilitating the disease progression. Use of combinations of cancer drugs, sequential therapy, adaptive therapy and topical ablation of drug-resistant malignant lumps may help to prolong the time to treatment failure. Many studies on mechanisms of drug resistance rely on the use of cell cultures and animal models. The development of approaches that allow efficient monitoring of the evolution of tumor phenotype in clinical setting presents a challenge.



中文翻译:

获得性肿瘤耐药的机制

全身疗法通常会导致肿瘤缩小,但很少能成功根除所有癌细胞。药物外流,癌症干细胞(CSCs)的持久性,上皮-间质转化(EMT)和细胞凋亡的下调是治疗失败的最普遍原因。肿瘤从靶向化合物中逃逸通常涉及特定于途径的机制,这导致受影响的信号级联反应得以恢复。耐药性的获得是由突变,基因表达的变化,选择性剪接,翻译后蛋白质修饰等介导的。对治疗的耐药性可能未必涉及新的肿瘤克隆的出现:多项研究表明,即使是化学性肿瘤也已经存在细胞很少 能够抵抗治疗压力并促进疾病进展。结合使用抗癌药物,序贯治疗,适应性治疗和局部消融耐药性恶性肿块可能有助于延长治疗失败的时间。关于耐药机制的许多研究都依赖于细胞培养物和动物模型的使用。允许在临床环境中有效监测肿瘤表型演变的方法的发展提出了挑战。

更新日期:2019-08-20
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