Cetuximab [the epidermal growth factor receptor (EGFR)-targeting mAb] improves clinical outcomes when added to standard chemotherapy used in the treatment of metastatic colorectal cancer. Patients with hotspot mutations in Kirsten rat sarcoma viral oncogene (KRAS) mutation in exon 2 were not recommended to be treated with cetuximab. However, there is still a lack of clinical data for those unreported non-hotspot KRAS mutations in exon 2 and their response to cetuximab. In this study, we reported a 35-year-old woman who was diagnosed with stage IVA CRC with liver metastases. An exceptionally uncommon KRASP34R mutation in KRAS exon 2 was detected in tumor specimens by next-generation sequencing. This patient obtained limited benefit from first-line chemotherapy and did not respond to cetuximab in the second-line course. In the third-line course, the patient also did not respond to the combination treatment of furaquitinib and cindilimab. The patient died 8 months after treatment initiation. In this study, we found amplification of the rare oncogenic KRASP34R was not only associated with an aggressive phenotype, but also supported cancer resistance to cetuximab, chemotherapy, and immunotherapy.

中文翻译：

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西妥昔单抗治疗患有新型 KRAS P34R 的转移性结直肠癌患者的病例报告结果。

西妥昔单抗 [表皮生长因子受体 (EGFR) 靶向单克隆抗体] 添加到用于治疗转移性结直肠癌的标准化疗中可改善临床结果。克尔斯滕大鼠肉瘤病毒癌基因（KRAS）外显子2发生热点突变的患者不建议接受西妥昔单抗治疗。然而，对于那些未报道的外显子2非热点KRAS突变及其对西妥昔单抗的反应仍缺乏临床数据。在这项研究中，我们报道了一名 35 岁女性，她被诊断患有 IVA 期 CRC 并伴有肝转移。通过新一代测序在肿瘤样本中检测到 KRAS 外显子 2 中异常罕见的 KRASP34R 突变。该患者从一线化疗中获得的益处有限，并且在二线疗程中对西妥昔单抗没有反应。在三线疗程中，患者对呋喃替尼和辛迪利单抗联合治疗也没有反应。患者在治疗开始后 8 个月死亡。在这项研究中，我们发现罕见致癌基因 KRASP34R 的扩增不仅与侵袭性表型相关，而且还支持癌症对西妥昔单抗、化疗和免疫疗法的耐药性。