Functional and genomic analyses reveal therapeutic potential of targeting β-catenin/CBP activity in head and neck cancer

Genome Medicine
Vinay K KarthaMaria A Kukuruzinska

Abstract

Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy characterized by tumor heterogeneity, locoregional metastases, and resistance to existing treatments. Although a number of genomic and molecular alterations associated with HNSCC have been identified, they have had limited impact on the clinical management of this disease. To date, few targeted therapies are available for HNSCC, and only a small fraction of patients have benefited from these treatments. A frequent feature of HNSCC is the inappropriate activation of β-catenin that has been implicated in cell survival and in the maintenance and expansion of stem cell-like populations, thought to be the underlying cause of tumor recurrence and resistance to treatment. However, the therapeutic value of targeting β-catenin activity in HNSCC has not been explored. We utilized a combination of computational and experimental profiling approaches to examine the effects of blocking the interaction between β-catenin and cAMP-responsive element binding (CREB)-binding protein (CBP) using the small molecule inhibitor ICG-001. We generated and annotated in vitro treatment gene expression signatures of HNSCC cells, derived from human oral squamous cell carcinomas (OSCCs)...Continue Reading

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Citations

Jan 8, 2019·Journal of Dental Research·M V Bais
Oct 2, 2020·Molecular Medicine Reports·Liya JiangJun Lin
Nov 20, 2020·Cellular Oncology (Dordrecht)·Caterina Peraldo-NeiaGiovanna Chiorino
Jan 21, 2021·Frontiers in Molecular Biosciences·Jing XieDa-Li Zheng
Feb 17, 2021·Signal Transduction and Targeted Therapy·He-Ming ZhouQin Li
Aug 7, 2021·Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology·Robert Kleszcz, Jarosław Paluszczak

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Methods Mentioned

BETA
xenografts
FCS
xenograft
flow cytometry
confocal
fluorescence-activated cell sorting
Chip
RNASeq
confocal microscopy
PCR

Software Mentioned

Gene Set Enrichment Analysis ( GSEA
PRISM GraphPad
FACSDiva
affy R
GraphPad Prism
BD FACSDiva
ASSIGN
FlowJo
incuCyte
GSEA

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