PDF(Pubmed)
Abstract：
Colorectal cancer (CRC) is currently one of the most common tumor types diagnosed worldwide. In the early stages, the disease responds well to surgical and chemotherapeutic treatment, but in the later stages when therapeutic options are exhausted, comprehensive genomic profiling can guide further treatment decisions. We present the case of a 46-year-old man of Ashkenazi Jewish ancestry who was diagnosed with KRAS-mutated metastatic colorectal cancer. After surgery and progression on standard FOLFOX/FOLFIRI + bevacizumab therapy, as well as on Trifluridine/Tipiracil, comprehensive genomic profiling was performed with the hope of expanding therapeutic options. Following comprehensive tumor molecular profiling via NGS, a discussion of the case was discussed at the local molecular tumor board in order to determine further treatment strategy. An activating variant of KRAS and PIK3CA, FLT3 and SRC amplification and damaging TP53 and APC variants were discarded by MTB as potential targetable biomarkers. The BRCA2 p.S1415fs*4 founder frameshift variant was of interest and the patient was included in the clinical trial investigating the efficacy of a PARP inhibitor talazoparib. Unfortunately, the disease progression was detected within one month of talazoparib treatment and the patient died during the 8th cycle of FOLFIRI + bevacizumab therapy rechallenge.
摘要：
结直肠癌（CRC）是目前全球诊断最常见的肿瘤类型之一。在早期阶段,这种疾病对手术和化疗治疗反应良好，但是在治疗方案用尽的后期，全面的基因组分析可以指导进一步的治疗决策.我们介绍了一名46岁的Ashkenazi犹太血统男子，他被诊断患有KRAS突变的转移性结直肠癌。在标准FOLFOX/FOLFIRI+贝伐单抗治疗的手术和进展后，以及氟尿苷/替匹拉嘧啶，我们进行了全面的基因组分析,以期扩大治疗选择.通过NGS进行全面的肿瘤分子谱分析，在当地分子肿瘤委员会对该病例进行了讨论,以确定进一步的治疗策略.KRAS和PIK3CA的激活变体，FLT3和SRC扩增和破坏性TP53和APC变体作为潜在的可靶向生物标志物被MTB丢弃。BRCA2p.S1415fs*4创始人移码变体引起了人们的兴趣，该患者被纳入了研究PARP抑制剂talazoparib疗效的临床试验。不幸的是,在talazoparib治疗后1个月内检测到疾病进展,患者在FOLFIRI+贝伐单抗治疗再激发的第8个周期中死亡.
