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Gene expression profiles of ibrutinib-responsive and ibrutinib non-responsive cells in ERBB4 expressing cancer cell lines

ABSTRACT: By using a unique functional protein microarray platform, we found that the FDA approved drug ibrutinib can inhibits ERBB4 activity in the same nM range as its canonical target, BTK. Cell-based assays revealed that ibrutinib treatment inhibited cell growth in some ERBB4 expressing cancer cells whereas no response was observed in other cells. Therefore, to identify global gene expression differences between ibrutinib responsive and non-responsive cancer cells, we performed RNA-Seq, and identified a signature featuring the WNT pathway that predicts growth responsiveness to ibrutinib in ERBB4 expressing cancers. Overall design: Examination of gene expression profiles of 4 ibrutinib responsive and 4 ibrutinib non-responsive ERBB4 expressing cancer cell lines

INSTRUMENT(S): Illumina HiSeq 2000 (Homo sapiens)

SUBMITTER: Joshua LaBaer 

PROVIDER: GSE102744 | GEO | 2018-02-07


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Ibrutinib inhibition of ERBB4 reduces cell growth in a WNT5A-dependent manner.

Rauf Femina F   Festa Fernanda F   Park Jin G JG   Magee Mitchell M   Eaton Seron S   Rinaldi Capria C   Betanzos Carlos Morales CM   Gonzalez-Malerva Laura L   LaBaer Joshua J  

Oncogene 20180205 17

Alterations in ERBB family members have been associated with many tumor malignancies. EGFR and ERBB2 have been extensively explored in clinical oncology and several drugs currently target them therapeutically. However, the significance of ERBB4 as a potential therapeutic target remains mostly unexplored, even though ERBB4 is overexpressed or mutated in many solid tumors. Using a unique functional protein microarray platform, we found that ibrutinib inhibits ERBB4 activity in the same nM range as  ...[more]

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