Oncotarget

Research Papers:

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 and Jeeyun Lee

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Oncotarget. 2017; 8:3237-3245. https://doi.org/10.18632/oncotarget.13700

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Abstract

Sung Hee Lim1,*, Sun-Young Kim1,*, Kyung Kim2, Hyojin Jang1, Soomin Ahn2, Kyoung-Mee Kim2, Nayoung K.D. Kim3, Woongyang Park3, Su Jin Lee1, Seung Tae Kim1, Se Hoon Park1, Joon Oh Park1, Young Suk Park1, Se-Hoon Lee1, Ho Yeong Lim1, Keunchil Park1, Won Ki Kang1, Jeeyun Lee1

1Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

2Department of Pathology and Translational Genomics, Sungkyunkwan University School of Medicine, Seoul, Korea

3Samsung Genome Institute, Samsung Medical Center, Seoul, Korea

*These authors have contributed equally to this work

Correspondence to:

Jeeyun Lee, email: [email protected]

Keywords: solid tumors, FLT3 amplification, regorafenib

Received: August 02, 2016    Accepted: November 15, 2016    Published: November 29, 2016

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.


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