Department of Gastroenterology and Hepatology, National Hospital Organization, Osaka National Hospital, Osaka, Japan.
Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Cancer Sci. 2021 Jan;112(1):314-322. doi: 10.1111/cas.14693. Epub 2020 Nov 20.
FMS-like tyrosine kinase 3 (FLT3) plays a key role in hematopoiesis. However, the oncogenic role of FLT3 amplification in patients with metastatic colorectal cancer (mCRC) remains unclear. Here, we aimed to evaluate the characteristics, prognosis, and treatment efficacy of an FLT3 inhibitor (regorafenib) in patients with mCRC with FLT3 amplifications. Tumor tissue samples from 2329 patients were sequenced using NGS in the Nationwide Cancer Genome Screening Project in Japan. The effects of clinicopathological features, co-altered genes, prognosis, and efficacy of regorafenib were investigated. Between April 2015 and June 2018, 85 patients with mCRC with FLT3 amplification were observed. There were no differences in baseline characteristics between patients with or without FLT3 amplification. The frequency of RAS or other gene co-alterations was inversely correlated with the copy number status. Median survival time in patients with FLT3 amplification was significantly shorter compared with those with non-FLT3 amplification. Further investigations of FLT3 amplification as a potential treatment target in mCRC are warranted.
FMS 样酪氨酸激酶 3(FLT3)在造血中发挥关键作用。然而,FLT3 扩增在转移性结直肠癌(mCRC)患者中的致癌作用尚不清楚。在这里,我们旨在评估在具有 FLT3 扩增的 mCRC 患者中使用 FLT3 抑制剂(regorafenib)的特征、预后和治疗效果。在日本全国癌症基因组筛查计划中,使用 NGS 对 2329 名患者的肿瘤组织样本进行了测序。研究了临床病理特征、共同改变的基因、预后和regorafenib 的疗效。2015 年 4 月至 2018 年 6 月,观察到 85 例具有 FLT3 扩增的 mCRC 患者。具有或不具有 FLT3 扩增的患者在基线特征方面没有差异。RAS 或其他基因共同改变的频率与拷贝数状态呈负相关。FLT3 扩增患者的中位生存时间明显短于非 FLT3 扩增患者。需要进一步研究 FLT3 扩增作为 mCRC 潜在治疗靶点的作用。