Imperial College London
Alternate

ProfessorCharlotteBevan

Faculty of Medicine, Department of Surgery & Cancer

Professor of Cancer Biology
 
 
 
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Contact

 

charlotte.bevan Website

 
 
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Assistant

 

Mrs Suzy Ford +44 (0)20 7594 2135

 
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Location

 

139ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Constantin:2023:10.1038/s41416-023-02252-8,
author = {Constantin, TA and Varela-Carver, A and Greenland, KK and de, Almeida GS and Olden, E and Penfold, L and Ang, S and Ormrod, A and Leach, DA and Lai, C-F and Ainscow, EK and Bahl, AK and Carling, D and Fuchter, MJ and Ali, S and Bevan, CL},
doi = {10.1038/s41416-023-02252-8},
journal = {British Journal of Cancer},
pages = {2326--2337},
title = {The CDK7 inhibitor CT7001 (Samuraciclib) targets proliferation pathways to inhibit advanced prostate cancer},
url = {http://dx.doi.org/10.1038/s41416-023-02252-8},
volume = {128},
year = {2023}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND: Current strategies to inhibit androgen receptor (AR) are circumvented in castration-resistant prostate cancer (CRPC). Cyclin-dependent kinase 7 (CDK7) promotes AR signalling, in addition to established roles in cell cycle and global transcription, providing a rationale for its therapeutic targeting in CRPC. METHODS: The antitumour activity of CT7001, an orally bioavailable CDK7 inhibitor, was investigated across CRPC models in vitro and in xenograft models in vivo. Cell-based assays and transcriptomic analyses of treated xenografts were employed to investigate the mechanisms driving CT7001 activity, alone and in combination with the antiandrogen enzalutamide. RESULTS: CT7001 selectively engages with CDK7 in prostate cancer cells, causing inhibition of proliferation and cell cycle arrest. Activation of p53, induction of apoptosis, and suppression of transcription mediated by full-length and constitutively active AR splice variants contribute to antitumour efficacy in vitro. Oral administration of CT7001 represses growth of CRPC xenografts and significantly augments growth inhibition achieved by enzalutamide. Transcriptome analyses of treated xenografts indicate cell cycle and AR inhibition as the mode of action of CT7001 in vivo. CONCLUSIONS: This study supports CDK7 inhibition as a strategy to target deregulated cell proliferation and demonstrates CT7001 is a promising CRPC therapeutic, alone or in combination with AR-targeting compounds.
AU  - Constantin,TA
AU  - Varela-Carver,A
AU  - Greenland,KK
AU  - de,Almeida GS
AU  - Olden,E
AU  - Penfold,L
AU  - Ang,S
AU  - Ormrod,A
AU  - Leach,DA
AU  - Lai,C-F
AU  - Ainscow,EK
AU  - Bahl,AK
AU  - Carling,D
AU  - Fuchter,MJ
AU  - Ali,S
AU  - Bevan,CL
DO  - 10.1038/s41416-023-02252-8
EP  - 2337
PY  - 2023///
SN  - 0007-0920
SP  - 2326
TI  - The CDK7 inhibitor CT7001 (Samuraciclib) targets proliferation pathways to inhibit advanced prostate cancer
T2  - British Journal of Cancer
UR  - http://dx.doi.org/10.1038/s41416-023-02252-8
UR  - https://www.ncbi.nlm.nih.gov/pubmed/37076563
UR  - https://www.nature.com/articles/s41416-023-02252-8
UR  - http://hdl.handle.net/10044/1/103960
VL  - 128
ER  -
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