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

doi:10.18632/oncotarget.13700

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

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

20 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 language	English
Pages (from-to)	3237-3245
Number of pages	9
Journal	Oncotarget
Volume	8
Issue number	2
DOIs	https://doi.org/10.18632/oncotarget.13700
State	Published - 2017

Keywords

FLT3 amplification
Regorafenib
Solid tumors

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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

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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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AU - Park, Joon Oh

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AU - Lee, Se Hoon

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AU - Kang, Won Ki

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

Abstract

Keywords

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