Kelleher Fergal C, Callaghan Grainne, Gallagher Catriona, O'Sullivan Hazel
Fergal C Kelleher, Department of Medical Oncology, Specialty Certification Medical Oncology Royal College of Physicians United Kingdom, European Certification in Medical Oncology, The Adelaide and Meath Hospital, 24 Dublin, Ireland.
World J Gastroenterol. 2017 May 7;23(17):3022-3029. doi: 10.3748/wjg.v23.i17.3022.
Colonic polyps may arise from BRAF inhibitor treatment of melanoma, possibly due to paradoxical activation of the mitogen-activated protein (MAP)-kinase pathway. In an alternative evidence based scenario, tubular colonic adenomas with gene mutations have also been identified in the context of BRAF inhibitor treatment, in the absence of mutations of genes. A minority of colorectal cancers develop by an alternative "serrated polyp pathway". This article postulates a novel hypothesis, that the established phenotypic and molecular characteristics of serrated colonic polyps/CRC offer an intriguing insight into the pathobiology of BRAF inhibitor induced colonic polyps. Serrated polyps are characterized by a CpG island methylation phenotype, silencing and cellular senescence. They also have mutations. The contention is that BRAF inhibitor induced polyps mimic the afore-described histology and molecular features of serrated polyps with the exception that instead of the presence of mutations they induce C-RAF homodimers and B-RAF: C-RAF heterodimers.
黑色素瘤的BRAF抑制剂治疗可能引发结肠息肉，这可能是由于丝裂原活化蛋白（MAP）激酶途径的反常激活所致。在另一种基于证据的情况下，在BRAF抑制剂治疗背景下，也发现了具有基因突变的管状结肠腺瘤，而不存在基因的突变。少数结直肠癌通过另一种“锯齿状息肉途径”发展而来。本文提出了一个新的假设，即锯齿状结肠息肉/结直肠癌已确立的表型和分子特征为BRAF抑制剂诱导的结肠息肉的病理生物学提供了有趣的见解。锯齿状息肉的特征是CpG岛甲基化表型、基因沉默和细胞衰老。它们也有基因突变。其论点是，BRAF抑制剂诱导的息肉模仿了上述锯齿状息肉的组织学和分子特征，不同之处在于它们不是存在基因突变，而是诱导C-RAF同二聚体和B-RAF：C-RAF异二聚体。
