Anne Kiltie BM, BCh, MA, DM, MRCP(UK), FRCR
- Cancer and Haematology
- Dr Martin Kerr, PhD
- Dr Eva McGrowder, PhD
- Ms Naomi Sharma, PhD, Intermediate Clinical Fellow
- Dr Blaz Groselj, DPhil Student
- Ms Sarah Jevons, DPhil Student
- Ms Alexa Walker, DPhil Student
- Ms Katalin Karaszi, Research Technician
- Ms Helen Scott, Research Technician
- Groselj Blaz, Kerr Martin, and Kiltie Anne E (2013) Radiosensitisation of bladder cancer cells by panobinostat is modulated by Ku80 expression. Radiother Oncol.
- Qiao Boling, Kerr Martin, Groselj Blaz, Teo Mark TW, Knowles Margaret A, Bristow Robert G, Phillips Roger M, and Kiltie Anne E (2013) Imatinib radiosensitizes bladder cancer by targeting homologous recombination. Cancer Res, 73(5):1611-20.
- Teo Mark TW, Landi Debora, Taylor Claire F, Elliott Faye, Vaslin Laurence, Cox David G, Hall Janet, Landi Stefano, Bishop D T, and Kiltie Anne E (2012) The role of microRNA-binding site polymorphisms in DNA repair genes as risk factors for bladder cancer and breast cancer and their impact on radiotherapy outcomes. Carcinogenesis, 33(3):581-6.
- Choudhury A, Swindell R, Logue J P, Elliott P A, Livsey J E, Wise M, Symonds P, Wylie J P, Ramani V, Sangar V, Lyons J, Bottomley I, McCaul D, Clarke N W, Kiltie A E, and Cowan R A (2011) Phase II Study of Conformal Hypofractionated Radiotherapy With Concurrent Gemcitabine in Muscle-Invasive Bladder Cancer. J Clin Oncol.
- Choudhury A, Nelson LD, Teo MT, Chilka S, Bhattarai S, Johnston C, Elliott F, Lowery J, Taylor CF, Churchman M, Bentley J, Knowles MA, Harnden P, Bristow RG, Bishop DT, and Kiltie AE (2010) MRE11 expression is predictive of cause-specific survival following radical radiotherapy for muscle invasive bladder cancer Cancer research, 15:7017:7026.
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Aberrant DNA double strand repair mechanisms in bladder cancer
The development of breaks in both strands of DNA (DNA double-strand breaks) is a normal part of cell division and differentiation. Accurate repair of these breaks is essential to maintain genome stability, preventing replication and propagation of DNA with genomic mistakes. Pathways that repair DNA double strand breaks have been identified and include homologous recombination (HR), non-homologous end joining (NHEJ) and a less well understood repair mechanism, microhomology-mediated end joining (MMEJ). MMEJ is a pathway particularly prone to errors and as a result can cause increased levels of chromosomal translocations and deletions, contributing to an increase in oncogenic chromosome rearrangements that are the hallmark of cancer cells. One of the key areas of research focus is to investigate the mechanisms underlying the defective NHEJ and the MMEJ mechanisms seen in muscle invasive bladder cancer, and to exploit this clinically in combined radiotherapy/biological treatments. Such exploitation could include targeting of HR, to increase the therapeutic ratio. They tyrosine kinase inhibitor imatinib and the histone deacetylase inhibitor panobinostat have shown promise in this regard.
DNA damage signalling proteins as biomarkers for radiotherapy and chemotherapy effectiveness in bladder cancer
There are currently limited data comparing surgery and radiotherapy with or without concurrent chemotherapy for treatment of muscle invasive bladder cancer and selection of therapy is currently based on patient choice with recommendations from their urologist and oncologist. Identifying which patients are likely to benefit from radiotherapy would help to rationalise its use in the management of these patients. Earlier studies have demonstrated that patients who have a higher expression of the DNA damage signalling protein MRE11 have improved survival after radiotherapy compared with those with low expression levels, indicating that MRE11 is a biomarker for radiotherapy outcome in muscle invasive bladder cancer. Current research is focussed on developing and validating a clinically-useful assay for MRE11, in collaboration with the Paterson Institute in Manchester, Leeds Institute of Molecular Medicine and the University of Birmingham, and to establish the role of other such biomarkers. As part of the validation process, potential biomarkers are being tested using tissue samples from large UK bladder cancer radiotherapy randomised trials (BCON and BC2001) and successful biomarkers and assays will then be tested in randomised controlled clinical trials. This should ultimately allow patient selection for optimal bladder cancer treatment, thus increasing overall cure rates.
Muscle invasive bladder cancer is treated primarily with surgical removal of the bladder (cystectomy) or radical radiotherapy. Bladder-preserving treatments include radiotherapy given together with the chemotherapy cisplatin. However, many elderly or unfit patients may not be able to tolerate the toxicity of cisplatin and an alternative in these patients is the chemotherapy gemcitabine (given at a lower dose than normal) in combination with radiotherapy, so-called GemX. At this dose, gemcitabine is believed to enhance radiotherapy by increasing the radiosensitivity of cancer cells. Studies have shown that GemX achieves a high response rate in patients with muscle invasive bladder cancer with long-lasting local control and acceptable toxicity, sparing patients from removal of their bladder. Being able to identify and predict which patients are most likely to benefit from GemX treatment would allow patient selection to optimise cure rates, spare likely non-responders from toxicity and allow them to be directed to potentially more effective treatments.
Gemtrans (measurement of gemcitabine metabolites in blood and urine as predictors of response to GemX bladder radiotherapy, NCT01343121) is a prospective observational feasibility study that is testing the hypothesis that plasma, peripheral blood mononuclear cell and urine levels of gemcitabine and its metabolites predict response to GemX chemoradiation at first check cystoscopy (a medical procedure used to examine the bladder) which is done three months after radiotherapy. In the longer term Gemtrans will also evaluate any potential impact of MRE11 expression and expression of gemcitabine metabolizing enzymes on the study results and clinical outcome. Molecular analysis will also be undertaken to see whether there are any genetic variations that are associated with expression patterns or outcome.
Dr Anne Kiltie is a Clinical Group Leader at the Gray Institute for Radiation Oncology and Biology within the University of Oxford. She is also an Honorary Consultant Clinical Oncologist at Oxford University NHS Trust.
Dr Kiltie joined the University of Oxford in October 2009 after eight years as a Senior Lecturer/Honorary Consultant Clinical Oncologist (Radiotherapist) at St James's University Hospital and Leeds Institute of Molecular Medicine, Leeds (Nov 2001 - Sept 2009). Prior to that she was a Clinical Research Fellow at the Imperial Cancer Research Fund (ICRF) Clare Hall Laboratories in Hertfordshire (Oct 1999 - Oct 2001).
Dr Kiltie is a member of several professional organisations including the Royal College of Radiologists, ESTRO, the British Association of Urological Surgeons and the British Uro-oncology Group. She has authored or co-authored 47 publications and been invited to present her work at national and international conferences.
October 2009 to present Clinical Group Leader, Gray Institute for Radiation Oncology and Biology, University of Oxford and Honorary Consultant Clinical Oncologist, Oxford Radcliffe NHS Trust.
Nov 2001 - Sept 2009 Senior Lecturer/Honorary Consultant Clinical Oncologist (Radiotherapist), St James's University Hospital and St James's Institute of Oncology, Leeds.
Oct 1999 - Oct 2001 Clinical Research Fellow, ICRF Clare Hall Laboratories, South Mimms, Herts.
Awards, Training and Qualifications
2006 Cancer Research UK Clinician Scientist Fellowship.
1998 ESTRO Varian Radiobiology Research Award.
1999 DM, University of Oxford
1995 FRCR (Clinical Oncology)
1992 MRCP (UK)
1989 MA, Sidney Sussex College, Cambridge University
1988 BM BCh, Oxford University Medical School
1985 BA, Sidney Sussex College, Cambridge University