University of Toronto, Department of Immunology, Toronto, Ontario, Canada.
University of Toronto, Department of Immunology, Toronto, Ontario, Canada.
Trends Mol Med. 2016 Apr;22(4):274-289. doi: 10.1016/j.molmed.2016.02.003. Epub 2016 Mar 9.
Colorectal cancer (CRC) remains one of the most prevalent cancers worldwide. In sporadic CRC, mutations frequently occur in the DNA mismatch repair (MMR) pathway. In addition, germline MMR mutations have been linked to Lynch syndrome, the most common form of hereditary CRC. Although genetic mutations, diet, inflammation, and the gut microbiota can influence CRC, it is unclear how MMR deficiency relates to these factors to modulate disease. In this review, the association of MMR to the etiology of CRC is examined, particularly in the context of microRNAs (miRNAs), inflammation, and the microbiome. We also discuss the most current targeted therapies, methods of prevention, and molecular biomarkers against MMR-deficient CRC, all of which are encouraging advancements in the field.
结直肠癌(CRC)仍然是全球最常见的癌症之一。在散发性 CRC 中,DNA 错配修复(MMR)途径经常发生突变。此外,种系 MMR 突变与林奇综合征有关,林奇综合征是最常见的遗传性 CRC 形式。尽管遗传突变、饮食、炎症和肠道微生物群可以影响 CRC,但尚不清楚 MMR 缺乏如何与这些因素相关以调节疾病。在这篇综述中,我们研究了 MMR 与 CRC 病因的关联,特别是在 microRNAs(miRNAs)、炎症和微生物组的背景下。我们还讨论了针对 MMR 缺陷型 CRC 的最先进的靶向治疗方法、预防方法和分子生物标志物,所有这些都是该领域令人鼓舞的进展。