结直肠癌的精准医学:大数据和微进展的时代

Precision medicine for colorectal cancer: a big data and micro-progress era

依据大数据为基础的结直肠癌精准医学是一个有吸引力的研究方向。虽然下一代测序(next generation sequencing,NGS)技术发展迅速,但科学和实践方面的挑战导致临床上进展微小。最大的挑战是驱动突变的识别,因为除了EGFR、MLH1、PIK3CA和KRAS基因异常,结直肠癌没有其他有效的致癌驱动突变存在。发展生物信息学工具,超深度测序和监测循环肿瘤DNA(circulating tumor DNA,ct DNA)方法,以帮助确定发生率微小的驱动突变,以及评估通路的激活,并进行联合治疗的方法,有助于在将来解决上述问题。大多数候选基因组改变的发生率微小,限制了精准医学的临床实践。解决策略是发展个体化的篮子试验或雨伞试验。

Precision medicine based on big data is an attractive research field in colorectal cancer.Though the next generation sequencing (NGS) technology has developed rapidly, the challenges from science and practice aspects make the clinical progress fairly slow. In addition to EGFR, MLH1, PIK3CA and KRAS gene abnormalities, no other specific oncogenic driver mutations are found in colorectal cancer, so the biggest challenge is the identification of driver mutations. The development of bioinformatics tools, the application of deep sequencing and circulating tumor DNA (ctDNA) monitoring are helpful to determine rare driver gene mutation rate, assess pathways activation and combine different treatments, which can solve the above problems in future. The change in most candidate genomes is small, which hampers the clinical practice of precision medicine. Individual basket trial or umbrella trial may conquer the limitation.