English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

We previously found that therapeutic targetable fusions are detected across various cancers. To identify therapeutic targetable fusion in uterine cervical cancer, for which no effective gene targeted therapy has yet been clinically applied, we analyzed RNA sequencing data from 306 cervical cancer samples. We detected 445 high confidence fusion transcripts and identified four samples that harbored  FGFR3-TACC3  fusion as an attractive therapeutic target. The frequency of  FGFR3-TACC3 -fusion-positive cervical cancer is also 1.9% (2/103) in an independent cohort. Continuous expression of the  FGFR3-TACC3  fusion transcript and protein induced anchorage-independent growth in the cervical epithelial cell line established from the ectocervix (Ect1/E6E7) but not in that from endocervix (End1/E6E7). Injection of  FGFR3-TACC3  fusion-transfected-Ect1/E6E7 cells subcutaneously into NOG mice generated squamous cell carcinoma xenograft tumors, suggesting the association between  FGFR3-TACC3  fusion and squamous cell carcinogenesis. Transfection of a  FGFR3-TACC3  fusion transcript into four cervical cancer cell lines (SiHa, ME180, HeLa, and Ca Ski) induced activation of the MAPK pathway and enhancement of cell proliferation. Transcriptome analysis of the  FGFR3-TACC3  fusion-transfected cell lines revealed that an  IL8 -triggered inflammatory response was increased, via activation of FGFR3–MAPK signaling. Continuous expression of  FGFR3-TACC3  fusion led to activation of the PI3K–AKT pathway only in the two cell lines that harbored  PIK3CA  mutations. Sensitivity to the  FGFR  inhibitor, BGJ398, was found to depend on  PIK3CA  mutation status. Dual inhibition of both FGFR and AKT showed an obvious synergistic effect in cell lines that harbor mutant  PIK3CA . Additionally, TACC3 inhibitor, KHS101, suppressed FGFR3-TACC3 fusion protein expression and showed antitumor effect against  FGFR3-TACC3  fusion-transfected cell lines.  FGFR3-TACC3  fusion-positive cancer has frequent genetic alterations of the PI3K/AKT pathway and selection of appropriate treatment based on PI3K/AKT pathway status should be required.

Novel therapeutic strategy for cervical cancer harboring FGFR3-TACC3 fusions