有K-ras突变的结直肠癌不能再用.PPT

临床意义 MSI-H CRC Proximal colonic location Mucinous and undifferentiated histology Crohn’s lymphoid reaction Better prognosis Usually without liver metastasis And expansile growth pattern MSI-H colorectal cancer: special histologic types mucinous signet ring cell medullary 六.K-ras突变的检测 K-ras突变的检测在应用抗EGFR抗体靶向治疗时必须要做，盲目用药不仅费用高还有毒副作用，而且以后还会有医疗纠纷。 有K-ras突变的结直肠癌不能再用 （cetuximab,panitumumab）。 B-raf V600E突变的检测也列入NCCN标准。最近基本肯定B-raf V600E突变的病例也不能用这种靶向治疗。 KRAS status 与靶向治疗 July 2008 the european medicines evaluation agency has extended the approval for cetuximab to any line of treatment and any fluoropyrimidine-based chemotherapy combination in mCRC, but only in patients with a wild-type KRAS tumor. January 2009, American Society of Clinical Oncology published guidelines that strongly support the use of anti-EGFR drugs in mCRC only in patients with wild-type KRAS. KRAS 是EGFR信号传导下游的重要分子 K-ras 突变病人不适合于EGFR 抑制剂治疗 具有野生型 KRAS 基因的病人对EGFR 抑制剂治疗反应，明显延长生存时间 KRAS 突变检测确定EGFR 抑制剂治疗 K-RAS 突变 和 EGFR 抗体治疗 K-RASwt MEK Elk Raf EGFR EGFR ERK Normal Colon mucosa: EGFR not activated K-RAS unmutated (K-RASwt) K-RASwt MEK Elk Raf EGFR EGFR ERK Colon carcinomas: EGFR activated 60% K-RAS unmutated (K-RASwt) K-RAS 突变和 EGFR抗体治疗 K-RASwt MEK Elk Raf EGFR EGFR ERK Cetuximab/Panitumumab inhibit EGFR/K-RAS signal transduction K-RAS 突变 和 EGFR 抗体治疗 西妥昔单抗 MEK Elk ERK Raf aktiv EGFR EGFR 40% of colon carcinomas: EGFR activated, but K-RAS mutated (K-RASmut) K-RASmut K-RASwt MEK Elk Raf EGFR EGFR ERK K-RAS 突变 和 EGFR 抗体治疗 Cetuximab/Panitumumab inhibit EGFR/K-RAS K-RASwt MEK Elk Raf EGFR EGFR ERK MEK Elk ERK Raf aktiv EGFR EGFR Cetuximab/Panitumumab inefficious K-RASmut K-RAS 突变 和 EGFR 抗体治疗 Cetuximab/Panitumumab inhibit EGFR/K-RAS K-RASwt MEK Elk Raf EGFR EGFR ERK Cetuximab/Panitumumab wirkungslos ca. 40% der Patienten EGFR EGFR MEK Elk Rasmut Karapetis CS et al. NEJM 2008 K-RAS 突变 和 EGFR 抗体治疗 Cetuximab/Panitumumab inhibit EGFR/K-RAS 西妥昔治疗肝转移 治疗前 治疗后 Dr