Perona R, Sánchez-Pérez I
Instituto de Investigaciones Biomédicas CSIC-UAM, C/Arturo Duperier, 4, Madrid 28029, Spain.
Br J Cancer. 2004 Feb 9;90(3):573-7. doi: 10.1038/sj.bjc.6601552.
Despite the combined action of surgery, radiotherapy and chemotherapy, the leading cause of death in cancer patients continues to be the acquired, or intrinsic, tumour resistance to therapy. Some of the genetic alterations that contribute to the malignant transformation are involved in maintaining cell survival under uncontrolled growth conditions. Chemotherapy agents, as well as radiotherapy, trigger a series of signalling pathways in the cells that activate not only the apoptotic machinery, but also cell-survival pathways. In this scenario, the efficacy of therapy is the result of balance between the apoptotic and the survival pathways activated in the tumour, and those elicited by the therapeutic agent. Apoptosis is one of the programmes usually altered in most cancers so as to guarantee tumour progression and, often, these alterations are responsible for therapy resistance, as well.
尽管手术、放疗和化疗联合应用,但癌症患者的主要死因仍然是肿瘤对治疗产生的获得性或内在性耐药。一些促成恶性转化的基因改变参与了在不受控制的生长条件下维持细胞存活。化疗药物以及放疗会触发细胞内一系列信号通路,这些通路不仅激活凋亡机制,还激活细胞存活通路。在这种情况下,治疗效果是肿瘤中激活的凋亡通路与存活通路之间以及治疗药物引发的通路之间平衡的结果。凋亡是大多数癌症中通常会改变的程序之一,以确保肿瘤进展,而且这些改变往往也是治疗耐药的原因。