Metadata supporting the article: Fibroblast growth factor receptor facilitates recurrence of minimal residual disease following trastuzumab emtansine therapy.
Creators: name: Akhand, Saeed S.
name: Chen, Hao
name: Purdy, Stephen Connor
name: Liu, Zian
name: Anderson, Joshua C.
name: Willey, Christopher D.
name: Wendt, Michael K.
Publisher: name: figshare
Year: 2020
Subjects: Biological Techniques
Cancer
Biological Sciences not elsewhere classified
Cancer Cell Biology
Cancer Genetics
Cancer Therapy (excl. Chemotherapy and Radiation Therapy)

description: Human epidermal growth factor receptor 2 (HER2)
is a member of the ErbB family of receptor tyrosine kinases. HER2-amplified
breast cancers respond to treatment with the HER2-targeted monoclonal
antibodies pertuzumab and trastuzumab at a high rate but acquired resistance to
these therapies remains a major clinical problem for patients with this breast
cancer subtype.<br>

Trastuzumab-emtansine (T-DM1) is an
antibody-drug conjugate (ADC) that efficiently delivers a highly potent microtubule
inhibitor to HER2 overexpressing cells. Intrinsic and acquired resistance to
T-DM1 is a significant clinical problem in breast cancer.

In the current study, the authors address
the hypothesis that fibroblast growth factor receptor 1 (FGFR) can act as a
driver of resistance to T-DM1.<br>

 

<b>Data access: </b>The datasets
generated and analysed during the current study are available from the
corresponding author, Dr. Michael Wendt (email address: mwendt@purdue.edu), upon reasonable request. Kinome data are
publicly available in supplementary table 1. Uncropped Western blots are
available as part of the supplementary information files. The Long-HER data set
analysed during the study, is publicly available in Gene Expression Omnibus: https://identifiers.org/geo:GSE44272.
<br>

<b>Approval for animal experiments: </b>All animal
experiments were conducted under institutional
animal care and use committee (IACUC) approval from Purdue
University.<br>

 

<b>Study aims and methodology: </b>In this study, the authors have<b> </b>utilised HER2 transformed human mammary epithelial cells (HME2), to address
the hypothesis that FGFR can act as a driver of resistance to T-DM1.

Bioluminescent, HER2-transformed HMLE
cells (HME2) were utilised.

HME2 cells (2x106) expressing firefly
luciferase were injected into the duct of the 4th mammary fat pad of female NRG
mice, as part of the xenograft studies.

The following are described in more
detail in the related article: cell culture and reagents, xenograft studies and
drug treatments, cell biological assays, immuno-assays, kinomic analyses and statistical
analyses.<b></b><br>

<b>Datasets supporting the findings in the article: </b>

Data supporting figure 1: <b>HME2-TDM1-volumes.xlsx</b> in .xlsx file
format 

Data supporting figure 2: <b>Par vs
TDM1R-TDM1(7-23-19).pzfx </b>in .pzfx file format

Data supporting figure 3: 4<b>4/24 binding.fcs</b>
in .fcs file format, GEO dataset: <b>GSE44272</b>, <b>HME2 FGFR1-TDM1 dose response.pzfx</b>
in .pzfx file format, and <b>trastuzumab binding.pzfx</b> in .pzfx file format.

Data supporting figure 4: <b>HME2-FGFR1-TDM1
in vivo.pzfx</b> in .pzfx file format.

Data supporting figure 5: <b>TDM1R-lap
response.pzfx</b>, <b>TDM1R-Afat respose.pzfx</b>, <b>LAPR-TDM1 response.pzfx</b> and <b>TDM1R FIIN4
reponse.pzfx</b>, are all in .pzfx file format.

Data supporting figure 6: <b>HME2 FIIN4
tumor growth.pzfx</b> and <b>HME2 tunel Ki-67.pzfx</b>, both in .pzfx file format.

Data supporting figure 7: <b>HCI-012
TDM1-FIIN4.pzfx</b> and <b>HCI-012 dose response.pzfx</b>, both in .pzfx file format.

<b>Kinome data</b> are available in .<b>xlsx</b> file
format in <b>supplementary table 1</b>.

<b>Uncropped Western blots</b> are available as
part of the <b>supplementary files</b> that accompany the article.<br>

 

<b>Software needed to access data: </b>The
GraphPad Prism 7 software is required to access the .pzfx files.<br>
Flow
Jo or any other flow cytometry software can be used to access the .fcs files.<b></b>