Indra Radek, Černá Věra
Department of Biochemistry, Faculty of Science, Charles University Albertov 6 128 00 Prague 2 Czech Republic
RSC Med Chem. 2025 May 27. doi: 10.1039/d5md00203f.
Cystic fibrosis (CF) is a life-limiting genetic disease that affects multiple organ systems. It is caused by a mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which results in the absence or damage of a relevant protein. If left untreated, it causes death in early childhood. The advent of more efficacious treatments has resulted in a notable increase in the life expectancy of CF patients. This has, in turn, led to an elevated risk of developing specific types of cancer. This review commences with an examination of CF from the standpoint of its etiology and therapeutic modalities. Subsequently, it presents a list of epidemiological studies that suggest an altered predisposition to certain cancers. A heightened risk is well documented, particularly in relation to the gastrointestinal tract. The following section addresses the role of CFTR in view of its potential involvement in the progression of various types of cancer. Several studies have indicated that the levels of the CFTR protein are reduced in many tumors and that this reduction is associated with the progression of the tumors. These decreased expressions are known to occur in the gastrointestinal tract, lungs, bladder, and/or prostate cancer. Conversely, ovarian, stomach, and cervical cancer are connected with its higher expression. The final section of the review focuses on the molecular mechanism of action of the CFTR protein in signaling pathways that affect cell proliferation and the process of carcinogenesis. This section attempts to explain the increased predisposition to cancer observed in patients with CF.
囊性纤维化（CF）是一种危及生命的遗传性疾病，会影响多个器官系统。它由囊性纤维化跨膜传导调节因子（CFTR）基因突变引起，该突变导致相关蛋白质缺失或受损。若不治疗，会导致儿童早期死亡。更有效治疗方法的出现使CF患者的预期寿命显著增加。这反过来又导致患特定类型癌症的风险升高。本综述首先从病因和治疗方式的角度对CF进行研究。随后，列出了一系列流行病学研究，这些研究表明患某些癌症的易感性发生了改变。患癌风险增加有充分记录，尤其是与胃肠道相关的风险。下一部分探讨CFTR在各类癌症进展中可能发挥的作用。多项研究表明，许多肿瘤中CFTR蛋白水平降低，且这种降低与肿瘤进展相关。已知这种表达降低发生在胃肠道、肺部、膀胱癌和/或前列腺癌中。相反，卵巢癌、胃癌和宫颈癌与其较高表达有关。综述的最后一部分重点关注CFTR蛋白在影响细胞增殖和致癌过程的信号通路中的分子作用机制。这部分试图解释CF患者中观察到的患癌易感性增加的现象。
