The implication of FLT3 amplification for FLT targeted therapeutics in solid tumors

Sung Hee Lim, Sun Young Kim, Kyung Kim, Hyojin Jang, Soomin Ahn, Kyoung Mee Kim, Nayoung K.D. Kim, Woongyang Park, Su Jin Lee, Seung Tae Kim, Se Hoon Park, Joon Oh Park, Young Suk Park, Se Hoon Lee, Ho Yeong Lim, Keunchil Park, Won Ki Kang, Jeeyun Lee

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6 Scopus citations

Abstract

We investigated the patients with solid cancers harboring Fms-like tyrosine kinase 3 (FLT3) amplification using targeted sequencing of tumor tissue specimen and FISH assay. Simultaneously, FLT3-amplified patient-derived cells (PDCs) were generated to evaluate the sensitivity to FLT3 inhibition. A patient with metastatic colon cancer who was previously treated with more than 3rd line cytotoxic chemotherapy was found to have FLT3 amplification and then received regorafenib showing partial response. In two PDC cell lines with FLT3 amplification, FLT3 mRNA expression was increased, however, the growth of tumor cells was not significantly inhibited by either regorafenib or sorafenib which is known to block the activity FLT3. Additional drug combinations with mTOR inhibitor did not affect the cell proliferation of PDC. FLT3 amplification in solid cancers is infrequently observed using targeted genomic profile, as yet, FLT3 amplification does not seem to be an actionable target or a proper biomarker for FLT3 inhibitor sensitivity.

Original languageEnglish
Pages (from-to)3237-3245
Number of pages9
JournalOncotarget
Volume8
Issue number2
DOIs
StatePublished - 1 Jan 2017

Keywords

  • FLT3 amplification
  • Regorafenib
  • Solid tumors

Cite this

Lim, S. H., Kim, S. Y., Kim, K., Jang, H., Ahn, S., Kim, K. M., Kim, N. K. D., Park, W., Lee, S. J., Kim, S. T., Park, S. H., Park, J. O., Park, Y. S., Lee, S. H., Lim, H. Y., Park, K., Kang, W. K., & Lee, J. (2017). The implication of FLT3 amplification for FLT targeted therapeutics in solid tumors. Oncotarget, 8(2), 3237-3245. https://doi.org/10.18632/oncotarget.13700