FMS-like tyrosine kinase 3 (FLT3) amplification in patients with metastatic colorectal cancer

Cancer Sci. 2021 Jan;112(1):314-322. doi: 10.1111/cas.14693. Epub 2020 Nov 20.

Abstract

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.

Keywords: FLT3 amplification; colorectal cancer; copy number status; next-generation sequencing; prognosis.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Female
  • Gene Amplification
  • Humans
  • Male
  • Middle Aged
  • Phenylurea Compounds / therapeutic use*
  • Pyridines / therapeutic use*
  • Retrospective Studies
  • Treatment Outcome
  • Young Adult
  • fms-Like Tyrosine Kinase 3 / genetics*

Substances

  • Antineoplastic Agents
  • Phenylurea Compounds
  • Pyridines
  • regorafenib
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3

Grants and funding