Genomes and Genes
Affiliation: University of Oxford
- Targeting angiogenesis in cancer: clinical development of bevacizumabDavid J Kerr
Clinical Pharmacology Department, Radcliffe Infirmary, Oxford, UK
Nat Clin Pract Oncol 1:39-43. 2004..This review highlights the key clinical trial data with bevacizumab and discusses the reasons for some of the contrasting results seen in different patient studies...
- Rofecoxib and cardiovascular adverse events in adjuvant treatment of colorectal cancerDavid J Kerr
Oncology Clinical Trials Office, University of Oxford, Oxford, United Kingdom
N Engl J Med 357:360-9. 2007..We report on cardiovascular adverse events in patients receiving rofecoxib to reduce rates of recurrence of colorectal cancer...
- Clinical development of gene therapy for colorectal cancerDavid Kerr
National Translational Cancer Research Network, Department of Clinical Pharmacology, Radcliffe Infirmary, Woodstock Road, Oxford OX2 6HE, UK
Nat Rev Cancer 3:615-22. 2003..Techniques include gene replacement, virus-directed enzyme-prodrug therapy, immune manipulation and virotherapy, all of which have entered clinical trials...
- Capecitabine/irinotecan combination regimens in colorectal cancerDavid J Kerr
University of Oxford, Department of Clinical Pharmacology, Radcliffe Infirmary, United Kingdom
Oncology (Williston Park) 16:27-9. 2002..Combinations of these agents therefore are being explored in patients with colorectal cancer. This report briefly reviews current and ongoing trials evaluating capecitabine/irinotecan combination regimens in treating this disease...
- Role of rare variants in undetermined multiple adenomatous polyposis and early-onset colorectal cancerJeremie H Lefevre
Department of Clinical Pharmacology, Cancer and Immunogenetics Laboratory, University of Oxford, Oxford, UK
J Hum Genet 57:709-16. 2012..2; 95% confidence interval=1.1-9.5; P=0.04). Rare variants are important risk factors in CRC and, as such, should be systematically assayed alongside common variation in the search for the genetic basis of complex diseases...
- Comprehensive assessment of variation at the transforming growth factor beta type 1 receptor locus and colorectal cancer predispositionLuis G Carvajal-Carmona
Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, United Kingdom
Proc Natl Acad Sci U S A 107:7858-62. 2010..We conclude that neither genetic variation nor ASE at TGFBR1 is likely to be a major CRC risk factor...
- 'Toxgnostics': an unmet need in cancer medicineDavid Church
1 Oxford Cancer Centre, Department of Oncology, University of Oxford, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LE, UK 2 Molecular and Population Genetics Laboratory, The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK
Nat Rev Cancer 14:440-5. 2014..Thus, we propose the new science of 'toxgnostics' (that is, the systematic, agnostic study of genetic predictors of toxicity from anticancer therapy). ..
- Hepatic arterial chemotherapy for colorectal cancer liver metastases: a review of advances in 2003Ray Chan
Department of Clinical Pharmacology, University of Oxford, Oxford, United Kingdom
Curr Opin Oncol 16:378-84. 2004..These new data will be reviewed in the context of previous trials and new observations of novel approaches involving HAC...
- Loss of expression of the double strand break repair protein ATM is associated with worse prognosis in colorectal cancer and loss of Ku70 expression is associated with CINAndrew D Beggs
University of Oxford, Oxford, UK
Oncotarget 3:1348-55. 2012..015). For Ku70, further studies are required to investigate the potential relationship of non-homologous end joining with chromosomal instability. Loss of ATM expression might serve as a biomarker of poor prognosis in colorectal cancer...
- Use of multivariate analysis to suggest a new molecular classification of colorectal cancerEnric Domingo
Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, UK
J Pathol 229:441-8. 2013..Our classification also showed potentially improved prognostic capabilities, with group 3, and possibly group 1, independently predicting disease-free survival...
- Capecitabine/irinotecan in colorectal cancer: European early-phase data and planned trialsDavid Kerr
National Translational Cancer Research Network, University of Oxford, Oxford, United Kingdom
Oncology (Williston Park) 16:12-5. 2002..These trials will help define the roles of this combination in the treatment of colorectal cancer...
- The nitroreductase/CB1954 enzyme-prodrug systemNicola K Green
Hybrid Systems Ltd, Littlemore Park, Oxford, UK
Methods Mol Med 90:459-77. 2004
- Cyclin D1 rare variants in UK multiple adenoma and early-onset colorectal cancer patientsCarolina Bonilla
Department of Clinical Pharmacology, University of Oxford, Headington, Oxford, UK
J Hum Genet 56:58-63. 2011..We conclude that rare variants of CCND1 are risk factors for colorectal cancer, with considerably larger effects than common polymorphisms, and as such should be systematically evaluated in susceptibility studies...
- Adjuvant chemotherapy for stage II colorectal cancer: the time is right!Rachel Midgley
Cancer Research UK Medical Oncology Unit, Churchill Hospital, Headington, Oxford, UK
Nat Clin Pract Oncol 2:364-9. 2005..Adjuvant therapy for stage II colon cancer has been more controversial. Recent trial data suggest, however, that there is a legitimate case for discussing the advantages and limitations with individual patients...
- Phase II studies of polymer-doxorubicin (PK1, FCE28068) in the treatment of breast, lung and colorectal cancerLeonard W Seymour
Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham, UK
Int J Oncol 34:1629-36. 2009....
- Capecitabine: have we got the dose right?Rachel Midgley
Department of Clinical Pharmacology, University of Oxford, Woodstock Road, Oxford, UK
Nat Clin Pract Oncol 6:17-24. 2009....
- Colorectal cancerShibani Nicum
Department of Clinical Pharmacology, The University of Oxford, Radcliffe Infirmary, Oxford, UK
Acta Oncol 42:263-75. 2003..The aim of this review is to provide an overview of the pathogenesis of CRC and to present the evidence base for chemotherapy and some of the novel strategies that are currently being evaluated in phase I and II trials...
- Intrahepatic arterial versus intravenous fluorouracil and folinic acid for colorectal cancer liver metastases: a multicentre randomised trialDavid J Kerr
Department of Clinical Pharmacology, University of Oxford, Radcliffe Infirmary, OX2 6HE, Oxford, UK
Lancet 361:368-73. 2003....
- Quinone oxidoreductase-2-mediated prodrug cancer therapyMark R Middleton
Department of Medical Oncology, Churchill Hospital, Headington, Oxford OX3 7LJ, UK
Sci Transl Med 2:40ra50. 2010..We detected DNA interstrand cross-links caused by nitroreduced CB1954 in tumor biopsies from treated patients, demonstrating that the activated prodrug exerts its cytotoxic properties through DNA base alkylation...
- Phase III randomized trial assessing rofecoxib in the adjuvant setting of colorectal cancer: final results of the VICTOR trialRachel S Midgley
Department of Clinical Pharmacology, University of Oxford, Headington, Oxford, United Kingdom
J Clin Oncol 28:4575-80. 2010..The purpose of this study was to test whether the COX-2 inhibitor rofecoxib could reduce recurrence and improve survival when administered in the adjuvant setting of colorectal cancer (CRC)...
- A trial of adjuvant therapy in colorectal cancer: the VICTOR trialStuart Pendlebury
Department of Clinical Pharmacology, Oxford University, UK
Clin Colorectal Cancer 3:58-60. 2003
- Immune enhancement of nitroreductase-induced cytotoxicity: studies using a bicistronic adenovirus vectorNicola K Green
Department of Clinical Pharmacology, University of Oxford, Radcliffe Infirmary, Oxford, United Kingdom
Int J Cancer 104:104-12. 2003....
- A candidate gene study of capecitabine-related toxicity in colorectal cancer identifies new toxicity variants at DPYD and a putative role for ENOSF1 rather than TYMSDan Rosmarin
Molecular and Population Genetics Laboratory, Oxford, UK Department of Oncology, University of Oxford, Old Road Campus Research Building, Oxford, UK
Gut 64:111-20. 2015..The few proven genetic biomarkers of 5-FU toxicity are rare variants and polymorphisms, respectively, at candidate loci dihydropyrimidine dehydrogenase (DPYD) and thymidylate synthase (TYMS)...
- Biomarkers in early-stage colorectal cancer: ready for prime time?David Church
Oxford Cancer Centre, University of Oxford, Oxford, UK
Dig Dis 30:27-33. 2012..However, the majority of these studies have been small and retrospective, reporting results that are highly likely to represent false positives. Consequently, their relevance to clinical practice requires definition...
- Chemotherapy for colorectal cancer in the metastatic and adjuvant setting: past, present and futureAmi Sabharwal
Cancer Research UK, Medical Oncology Unit, Churchill Hospital, Oxford, UK
Expert Rev Anticancer Ther 7:477-87. 2007..The evolution of chemotherapy use, current practice in the metastatic and adjuvant setting and possible future directions are discussed...
- Evolution of nonsurgical therapy for colorectal cancerRachel S Midgley
Department of Clinical Pharmacology, University of Oxford, Old Road Campus Research Building, Old Road, off Roosevelt Drive, Headington, Oxford, UK
Nat Clin Pract Gastroenterol Hepatol 6:108-20. 2009....
- Bevacizumab--current status and future directionsRachel Midgley
Department of Clinical Pharmacology and Cancer Therapeutics, Racliffe Infirmary, Woodstock Road, Oxford OX2 6HE, UK
Ann Oncol 16:999-1004. 2005..Questions still surround optimal dosing and the appropriate selection of patients who are most likely to benefit. Future trials will address these questions and provide further translational insights...
- Fine-mapping of colorectal cancer susceptibility loci at 8q23.3, 16q22.1 and 19q13.11: refinement of association signals and use of in silico analysis to suggest functional variation and unexpected candidate target genesLuis G Carvajal-Carmona
Wellcome Trust Centre for Human Genetics and Department of Clinical Pharmacology, University of Oxford, Oxford, UK
Hum Mol Genet 20:2879-88. 2011..In addition, caution should be exercised when assigning functionality to candidate genes in regions discovered through GWA analysis...
- Does chemotherapy given directly to the liver improve survival in patients with hepatic metastasis?David J Kerr
Department of Clinical Pharmacology, Radcliffe Infirmary, Woodstock Road, Oxford OX2 6HE, UK
Nat Clin Pract Oncol 3:480-1. 2006
- Common variation at the adiponectin locus is not associated with colorectal cancer risk in the UKLuis G Carvajal-Carmona
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
Hum Mol Genet 18:1889-92. 2009..We, therefore, failed to replicate an association between common variants at ADIPOQ and CRC risk in the UK, and suggest that the previous report is either population-specific or a false-positive result...
- Two errorsDavid J Kerr
Department of Clinical Pharmacology, Radcliffe Infirmary, Oxford OX2 6HE, UK
Lancet 364:907. 2004
- The challenge of cancer control in AfricaRebecca J Lingwood
Department for Continuing Education, University of Oxford, Littlegate House, 16 17 St Ebbes street, Oxford, OX1 1PT, UK
Nat Rev Cancer 8:398-403. 2008..Many of these cancers are preventable, or treatable when detected early enough. Establishing effective, affordable and workable cancer control plans in African countries is one step in the right direction toward limiting this epidemic...
- Regional hepatic chemotherapies in the treatment of colorectal cancer metastases to the liverThinn P Pwint
Medical Oncology Unit, Churchill Hospital, Oxford, UK
Semin Oncol 37:149-59. 2010..The regional strategies reviewed include portal venous infusion (PVI) of 5-fluorouracil (5-FU), intra-arterial chemotherapy (hepatic arterial infusion [HAI]), chemoembolization, and selective internal radiation therapy (SIRT)...
- Redesigning cancer careDavid Kerr
Department of Clinical Pharmacology, Universityof Oxford, Radcliffe Infirmary
BMJ 324:164-6. 2002..The cancer services collaborative is using improvement methods to reduce delays and improve the service for patients. The nine cancer networks using these methods have cut waiting times and improved patients' experiences of care...
- Gene profiling in early stage diseaseRachel Midgley
Department of Clinical Pharmacology, University of Oxford, Headington, Oxford, UK
Cancer J 16:210-3. 2010..58; 95% CI, 1.15-2.15; P = 0.004). This may become established as a prognostic tool of choice for stage II colon cancer...
- NTRAC pioneering a virtual modelDavid J Kerr
National Translational Cancer Research Network, University of Oxford, Department of Clinical Pharmacology, Radcliffe Infirmary, Woodstock Road, OX2 6HE, Oxford, UK
Lancet Oncol 4:393. 2003
- HR23B is a biomarker for tumor sensitivity to HDAC inhibitor-based therapyOmar Khan
Laboratory of Cancer Biology, Medical Sciences Division, University of Oxford, Oxford OX3 7DQ, United Kingdom
Proc Natl Acad Sci U S A 107:6532-7. 2010..Our study supports the personalized medicine approach for treating cancer and the increasing drive to translate laboratory-based findings into clinical utility...
- CB 1954: from the Walker tumor to NQO2 and VDEPTRichard J Knox
Enact Pharma PLC, Porton Down Scientific Park, Salisbury, Wiltshire, UK
Curr Pharm Des 9:2091-104. 2003..NQO2 activity is substantially raised in tumor samples from colorectal and hepatoma patients (up to 14-fold). A phase I clinical trial of an NQO2 co-substrate with CB 1954 is scheduled...
- Nitroreductase: a prodrug-activating enzyme for cancer gene therapyPeter F Searle
Cancer Research UK Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham
Clin Exp Pharmacol Physiol 31:811-6. 2004..These can provide improved cell sensitization to CB1954. Combinations of these are being tested. 7. The basis for a positive selection for improved NTR variants has been demonstrated...
- Virus-directed enzyme prodrug therapy: intratumoral administration of a replication-deficient adenovirus encoding nitroreductase to patients with resectable liver cancerDaniel H Palmer
Cancer Research UK Institute for Cancer Studies, Department of Pathology and Liver Research Laboratories, University of Birmingham, UK
J Clin Oncol 22:1546-52. 2004..In this study, we report the first clinical trial investigating the feasibility, safety, and transgene expression of a replication-defective adenovirus encoding nitroreductase (CTL102) in patients with liver tumors...
- Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised studyRichard Gray
Birmingham Clinical Trials Unit, University of Birmingham, Birmingham, UK
Lancet 370:2020-9. 2007..The aim of the QUASAR trial was to determine the size and duration of any survival benefit from adjuvant chemotherapy for patients with colorectal cancer at low risk of recurrence, for whom the indication for such treatment is unclear...
- Immunotherapy for colorectal cancerRachel S Midgley
Department of Health Clinician Scientist and Specialist Registrar Medical Oncology, Cancer Research UK, Churchill Hospital, Oxford
Expert Rev Anticancer Ther 3:63-78. 2003....
- Clinical experience with adenovirus in cancer therapyDaniel H Palmer
CR UK Institute for Cancer Studies, The Medical School, University of Birmingham, Edgbaston, UK
Curr Opin Mol Ther 4:423-34. 2002..It is anticipated that adenovirus-mediated gene therapy will be integrated with existing treatment modalities, including surgery, chemotherapy and radiotherapy, to facilitate improvement in cancer treatments in the future...
- Breast cancer cell-derived EMMPRIN stimulates fibroblast MMP2 release through a phospholipase A(2) and 5-lipoxygenase catalyzed pathwayPaul M Taylor
Cancer Research UK Institute for Cancer Studies, Birmingham University, Birmingham, B15 2TT, UK
Oncogene 21:5765-72. 2002..These results suggest that the production of soluble EMMPRIN, phospholipase A(2) and 5-lipoxygenase activities are sites for potential therapeutic intervention...
- Ras as a target in cancer therapyRachel S Midgley
CRC Institute for Cancer Studies, University of Birmingham, Birmingham, B15 2TT, Edgbaston, UK
Crit Rev Oncol Hematol 44:109-20. 2002..Though their clinical evaluation is still in infancy, these two modes of ras targeting represent rational therapeutic strategies that can undergo mechanistic evaluation in the clinic...
- Identification of FGF receptor-binding peptides for cancer gene therapyFukuto Maruta
Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham B15 2TT, UK
Cancer Gene Ther 9:543-52. 2002..These peptides should provide useful ligands for specific delivery of gene therapy vectors to clinically relevant targets...
- Single-dose clinical pharmacokinetic studies of gefitinibHelen C Swaisland
AstraZeneca Pharmaceuticals, Macclesfield, UK
Clin Pharmacokinet 44:1165-77. 2005....
- Gene therapy for colorectal cancerDaniel H Palmer
CRUK Institute for Cancer Studies, The Medical School, University of Birmingham, Vincent Drive, Edgbaston, Birmingham B15 2TF, UK
Br Med Bull 64:201-25. 2002..It is likely that gene therapy will be integrated into pre-existing therapies including surgery, chemotherapy and radiotherapy to establish its niche in tomorrow's medicine...
- Use of a phage display library to identify oligopeptides binding to the lumenal surface of polarized endothelium by ex vivo perfusion of human umbilical veinsFukuto Maruta
Cancer Research UK Institute for Cancer Studies, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
J Drug Target 11:53-9. 2003..These initial peptides may prove useful targeting agents for endothelial-selective delivery, and this powerful approach should be readily applicable to biopanning in a broad range of human vessels ex vivo...
- Bacteriophage biopanning in human tumour biopsies to identify cancer-specific targeting ligandsFukuto Maruta
Cancer Research UK Institute for Cancer Studies, University of Birmingham, and Department of Surgery, Selly Oak Hospital, UK
J Drug Target 15:311-9. 2007..This novel approach may be applicable to a wide range of settings, thus enabling iteration of consensus targeting sequences for tumour imaging and selective delivery of anticancer agents...
- A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancerJohn P Neoptolemos
Department of Surgery, Liverpool University, Liverpool, United Kingdom
N Engl J Med 350:1200-10. 2004..The effect of adjuvant treatment on survival in pancreatic cancer is unclear. We report the final results of the European Study Group for Pancreatic Cancer 1 Trial and update the interim results...
- Identification of oligopeptides binding to peritoneal tumors of gastric cancerNoriyuki Akita
Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan
Cancer Sci 97:1075-81. 2006..The peptide motif KLP seems a potential targeting ligand for the treatment of peritoneal metastasis of gastric cancer...
- Identification of an oligopeptide binding to hepatocellular carcinomaAkira Shimizu
Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan
Oncology 71:136-45. 2006..We carried out identification of a small peptide binding to human hepatocellular carcinoma (HCC) cells with the aim of applying the peptide for future HCC-targeted therapy or imaging...
- Hepatic drug targeting: phase I evaluation of polymer-bound doxorubicinLeonard W Seymour
Cancer Research UK Institute for Cancer Studies, University of Birmingham, United Kingdom
J Clin Oncol 20:1668-76. 2002..The present phase I study was devised to determine the toxicity, pharmacokinetic profile, and targeting capability of PK2...