Imperial College London
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ProfessorNagyHabib

Faculty of Medicine, Department of Surgery & Cancer

Professor of Hepatobiliary Surgery
 
 
 
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Contact

 

+44 (0)20 3313 8574nagy.habib

 
 
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Assistant

 

Mrs Benita White +44 (0)7960 986 387

 
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Location

 

BN1/18 B BlockHammersmith HospitalHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{McGuigan:2011,
author = {McGuigan, C and Habib, NA and Wasan, HS and Gabra, H and Jiao, LR and Slusarczyk, M and Chabot, JA and Saif, MW},
journal = {J Clin Oncol},
title = {A phosphoramidate ProTide (NUC-1031) and acquired and intrinsic resistance to gemcitabine.},
url = {http://www.ncbi.nlm.nih.gov/pubmed/28022714},
volume = {29},
year = {2011}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - e13540 Background: Resistance to gemcitabine is a major problem in the treatment of cancer. The key resistance mechanisms associated with gemcitabine are: lack of nucleoside transporters; lack of kinases for phosphorylation; and/or, rapid metabolism by deaminases. Resistance results in complete response rates of less than 10% in pancreatic cancer. The addition of a phosphoramidate ProTide moiety to gemcitabine enables: passive entry into the cell, by-passing the reliance on transporters; reduced reliance on kinases for phosphorylation; and, less susceptibility to deamination. METHODS: The ProTide (NUC-1031) was compared to the parent molecule (gemcitabine) in two pancreatic tumor xenograft models: Mia-Pa-Ca-2 (n=40), which is partially responsive to gemcitabine; and BxPC-3 (n=40), which is resistant. Two dose regimens for each tumor type were used, with NUC-1031 administered IP at doses of 0.076 or 0.19 mMol/kg when tumors had reached 150 - 200mm(3). The objective was to determine the ability of a novel agent (NUC-1031) to overcome gemcitabine resistance by measuring tumor growth in partially responsive and resistant pancreatic cell lines. RESULTS: The anti-tumor effect of NUC-1031 was greater and longer lasting than that of gemcitabine and control in both cell lines. NUC-1031 inhibition of tumor growth was significantly different from control in Mia-Pa-Ca-2 on days 4, 11, 14, 18, 21 and 25, and in BxPC-3 cells on days 25, 29, 33 and 37. In Mia-Pa-Ca-2 the tumor volume decreased immediately after first dosing and held at low levels until the end of the experiment. NUC-1031 was well tolerated and animals lost <2% body weight on treatment and this was regained rapidly after cessation of treatment. CONCLUSIONS: NUC-1031 showed statistically significant reduction in pancreatic tumor volume compared with gemcitabine and control. A phase I/II study of NUC-1031 in resistant/refractory pancreatic cancer is scheduled.
AU  - McGuigan,C
AU  - Habib,NA
AU  - Wasan,HS
AU  - Gabra,H
AU  - Jiao,LR
AU  - Slusarczyk,M
AU  - Chabot,JA
AU  - Saif,MW
PY  - 2011///
TI  - A phosphoramidate ProTide (NUC-1031) and acquired and intrinsic resistance to gemcitabine.
T2  - J Clin Oncol
UR  - http://www.ncbi.nlm.nih.gov/pubmed/28022714
VL  - 29
ER  -
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