Fernandez Harvey R, Varma Ashima, Flowers Sarah A, Rebeck George William
Department of Neuroscience, Georgetown University, Washington, DC 20057, USA.
Cancers (Basel). 2020 Dec 19;12(12):3842. doi: 10.3390/cancers12123842.
Cancer related cognitive impairment (CRCI) is a serious impairment to maintaining quality of life in cancer survivors. Cancer chemotherapy contributes to this condition through several potential mechanisms, including damage to the blood brain barrier, increases in oxidative stress and inflammation in the brain, and impaired neurogenesis, each of which lead to neuronal dysfunction. A genetic predisposition to CRCI is the E4 allele of the Apolipoprotein E gene (), which is also the strongest genetic risk factor for Alzheimer's disease. In normal brains, APOE performs essential lipid transport functions. The APOE4 isoform has been linked to altered lipid binding, increased oxidative stress and inflammation, reduced turnover of neural progenitor cells, and impairment of the blood brain barrier. As chemotherapy also affects these processes, the influence of on CRCI takes on great significance. This review outlines the main areas where genotype could play a role in CRCI. Potential therapeutics based on APOE biology could mitigate these detrimental cognitive effects for those receiving chemotherapy, emphasizing that the genotype could help in developing personalized cancer treatment regimens.
癌症相关认知障碍（CRCI）是癌症幸存者生活质量维持方面的一种严重障碍。癌症化疗通过多种潜在机制导致这种情况，包括对血脑屏障的损害、大脑氧化应激和炎症增加以及神经发生受损，每一种机制都会导致神经元功能障碍。CRCI的一个遗传易感性因素是载脂蛋白E基因的E4等位基因（），它也是阿尔茨海默病最强的遗传风险因素。在正常大脑中，APOE执行重要的脂质转运功能。APOE4亚型与脂质结合改变、氧化应激和炎症增加、神经祖细胞更新减少以及血脑屏障受损有关。由于化疗也会影响这些过程，因此APOE对CRCI的影响具有重要意义。本综述概述了APOE基因型可能在CRCI中发挥作用的主要领域。基于APOE生物学的潜在治疗方法可以减轻接受化疗者的这些有害认知影响，强调APOE基因型有助于制定个性化的癌症治疗方案。
