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Combination therapy with the CDK7 inhibitor and the tyrosine kinase inhibitor exerts synergistic anticancer effects against MYCN ‐amplified neuroblastoma by Tee, Andrew E.; Ciampa, Olivia C.; Wong, Matthew; Fletcher, Jamie I.; Kamili, Alvin; Chen, Jingwei; Ho, Nicholas; Sun, Yuting; Carter, Daniel R.; Cheung, Belamy B.; Marshall, Glenn M.; Liu, Pei Y.; Liu, Tao is a Medicine article available to read on EtoBox.
What is Combination therapy with the CDK7 inhibitor and the tyrosine kinase inhibitor exerts synergistic anticancer effects against MYCN ‐amplified neuroblastoma about?
Patients with neuroblastoma due to MYCN oncogene amplification and consequent N‐Myc oncoprotein overexpression have very poor prognosis. The cyclin‐dependent kinase 7 (CDK7)/super‐enhancer inhibitor THZ1 suppresses MYCN gene transcription, reduces neuroblastoma cell proliferation, but does not cause significant cell death. The protein kinase phosphatase 1 nuclear targeting subunit (PNUTS) has recently been shown to interact with c‐Myc protein and suppresses c‐Myc protein degradation. Here we screened the U.S. Food and Drug Administration‐Approved Oncology Drugs Set V from the National Cancer Institute, and identified tyrosine kinase inhibitors (TKIs), including ponatinib and lapatinib, as the Approved Oncology Drugs exerting the best synergistic anticancer effects with THZ1 in MYCN‐amplified neuroblastoma cells. Combination therapy with THZ1 and ponatinib or lapatinib synergistically induced neuroblastoma cell apoptosis, while having little effects in normal nonmalignant cells. Differential gene expression analysis identified PNUTS as one of the genes most synergistically reduced by the combination therapy. Reverse transcription polymerase chain reaction and immunoblot analyses con
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- Author
- Tee, Andrew E.; Ciampa, Olivia C.; Wong, Matthew; Fletcher, Jamie I.; Kamili, Alvin; Chen, Jingwei; Ho, Nicholas; Sun, Yuting; Carter, Daniel R.; Cheung, Belamy B.; Marshall, Glenn M.; Liu, Pei Y.; Liu, Tao
- Publisher
- John Wiley and Sons; Wiley (John Wiley & Sons); John Wiley & Sons Inc.; Wiley; Research Square; Test accounts (ISSN 0020-7136)
- Published
- 2020
- Language
- EN
- Field
- Medicine (Health Sciences)