oncology and genetics

Name: Dr Anthony Chalmers PhD FRCR

Academic position: Senior Lecturer and Honorary Consultant in Clinical Oncology

Research: Enhancing tumour radiosensitivity by targeting DNA repair proteins

Contact details:

Genome Damage and Stability Centre
University of Sussex
Falmer
Brighton BN1 9RQ
UK

Tel: +44 (0)1273 876637
Fax: +44 (0)1273 876121

E-mail:

Biography:

BA Hons (Physiological Sciences) 1989. Oxford University
BM BCh 1992. Oxford University Medical School
MRCP (UK)1995
FRCR (Clinical Oncology) 2000
Specialist Registrar in Clinical Oncology, Pan-Thames Rotation 1996 – 2004
PhD in Radiobiology with Profs. M C Joiner and M I Saunders, Gray Cancer Institute & University of London. 2000 – 2003
MRC Clinician Scientist Fellowship 2004
Senior Lecturer and Honorary Consultant in Clinical Oncology. Brighton and Sussex Medical School/Genome Damage and Stability Centre. 2004 – present.
MRC Senior Clinical Fellowship 2009

Research focus:

The effects of inhibiting individual DNA repair proteins on the radiosensitivity of human tumour cells: identifying promising therapeutic targets and elucidating the mechanisms and interactions responsible.

'The most exciting and challenging aspect of my work is to ensure that the groundbreaking scientific discoveries taking place in the Genome Damage and Stability Centre, one of the foremost DNA repair laboratories in the world, will result in improved treatment of cancer patients. I am particularly interested in developing new therapies for patients with malignant brain tumours because the existing treatments for these patients have limited success.’

For more information on the Genome Centre, please visit www.sussex.ac.uk/gdsc

Current research:

My previous work showed that inhibiting the activity of a DNA repair protein known as PARP-1 enhanced the ability of radiotherapy to inactivate rapidly dividing tumour cells, but had no effect upon non-dividing cells. This was a promising finding because brain tumour cells are rapidly dividing whereas normal brain cells rarely divide. Subsequent work has explored the mechanisms responsible for this effect, in particular the interactions of PARP-1 with other DNA repair proteins. Based on this work, we have designed a series of early phase clinical trials to test whether PARP inhibitors can be safely combined with radiotherapy and/or chemotherapy and used to treat patients with malignant brain tumours.

Recent developments in the field of cancer research have shown that many cancers contain a small population of cells that are capable of self-renewal and of initiating new tumours or tumour recurrence. In the case of malignant brain tumours, such cells have been termed ‘glioma stem cells’ and there is evidence that they are resistant to radiotherapy and perhaps chemotherapy. Because of the clinical importance of this finding, we have developed systems for culturing glioma stem cells in the lab and are currently examining how these cells respond to radiation and chemotherapy. Our aim is to identify drugs that will overcome the inherent resistance of these critical cells to current treatments.

Key/recent publications:

Review articles and editorials:

Chalmers AJ. The potential role and application of PARP inhibitors in cancer treatment. British Medical Bulletin 2009; 89:23-40.

Catt S, Chalmers A, Fallowfield L. Psychosocial and supportive-care needs in high-grade glioma. Lancet Oncology 2008; 9(9): 884-91.

Chalmers AJ, Radioresistant glioma stem cells - Therapeutic obstacle or promising target? DNA Repair (Amst) 2007; 6(9):1391-4.

Caldecott KW, Chalmers A. An Achilles' heel for breast cancer? Nat Struct Mol Biol. 2005; 12(5), 387-8.

Chalmers AJ. Poly(ADP-ribose) polymerase-1 and ionising radiation: sensor, signaller and therapeutic target. Clinical Oncology 2004; 16(1), 29-39.

Full papers:

Dungey FA, Caldecott KW, Chalmers AJ. Enhanced radiosensitization of human glioma cells by combining inhibition of PARP with inhibition of Hsp90. Mol Cancer Ther. 2009 Aug;8(8):2243-54. Epub 2009 Aug 11.

Chalmers AJ, Ruff EM, Martindale C, Lovegrove N, Short S. Cytotoxic effects of temozolomide and radiation are additive and schedule dependent. In Press, Int J Radiat Oncol Biol Phys

Chalmers AJ, Bentzen SM and Buffa, FM. A general framework for quantifying the effects of DNA repair inhibitors on radiation sensitivity as a function of dose. Theoretical Biology and Medical Modelling 2007; 4:25-31.

Chalmers AJ, Johnston PJ, Woodcock M, Joiner MC, Marples B. PARP-1, PARP-2 and cellular response to low doses of ionising radiation. Int J Radiat Oncol Biol Phys. 2004; 58(2), 410-9.

B. Marples, B.G. Wouters, S.J.Collis, A.J. Chalmers, and M.C. Joiner. Low dose Hyper-Radiosensitivity: A consequence of ineffective cell cycle arrest of radiation-damaged G2 phase cells. Radiat Res. 2004; 161(3), 247-55.

Teaching focus:

Cancer biology, especially radiobiology, and clinical oncology.

'The biology of cancer is fascinating in its own right and also serves as an ideal example for demonstrating the relationship between clinical treatment strategies and biological principles. In my teaching I aim to illustrate the relevance of past, current and future research with real clinical scenarios.'

Current/recent laboratory funding:

Medical Research Council (MRC) Senior Clinical Fellowship