The assessment of HER2 and other HER (ErbB) receptors by FRET to determine mechanisms of sensitivity and resistance to Herceptin (Trastuzumab) and other targeted therapies in breast cancer


Project Summary

Dr Kong’s work will focus on improving our understanding of the underlying mechanisms contributing to the poor response rate or resistance of patients to targeted therapies such as Herceptin, as well as developing mechanisms to better predict the success of these drugs in cancer patients. With the recent increase in the development and use of targeted therapies such as Herceptin, Iressa and Lapatinib in breast cancer, the ability to efficiently and quantifiably predict who will benefit most from these drugs will enable doctors to provide more tailored and cost effective therapy.

The project will involve assessing the activation of HER2 and other HER receptors by Fluorescence Resonance Energy Transfer (FRET) and Immunohistochemistry and to classify breast cancers based on the activation and dimerisation state of HER receptors. These results will be correlated with gene expression arrays to determine longer-term therapy and treatment strategies for breast cancer patients. Dr Kong and collaborators have recently been successful in securing access to samples from the HERA and Fin-Her Trials, which will greatly assist this work. It is anticipated that the work will establish FRET as a research and predictive tool for selection of patients in breast cancer trials who will most benefit from the drugs being investigated as well as potentially indicate new therapeutic targets.

Biography

Dr Anthony Kong MBBS MSc MRCP FRCR PhD
Dr Kong was born on the island of Borneo, coming the UK at the age of 16. He graduated from Barts and The London School of Medicine in 1997, taking the Sutton Prize in pathology and the ARC Prize in rheumatology.

Following his specialist training in clinical oncology at Barts, Anthony passed the fellowship exam of the Royal College of Radiologists in 2004 and was honoured with the prestigious Rohan Williams gold medal. Anthony then undertook a PhD, funded through a Cancer Research UK Clinician Training Fellowship, and under the supervision of Dr. Banafshe Larijani, Prof Peter Parker and Prof Adrian Harris.

Following his PhD, in 2007 he received a Mike Prize fellowship from the European Association for Cancer Research to do an IMRT clinical programme at the Cliniques Universitaires Saint-Luc in Brussels. After which he resumed his specialist training at the Royal Marsden Hospital in September 2007.

Anthony has received numerous prizes and awards for his doctoral research, including a Cancer Research UK pilot project award of £20,000 in 2005, Sylvia Lawler Prize from the Royal Society of Medicine in 2007, Applied Biosystems - EACR 40th Anniversary Research Award and Aflac-AACR Scholar-in-Training award in 2008.

Anthony will take up a Breakthrough Clinician Scientist Fellowship at the University of Oxford from 1 Sept 2008. He aims to build an academic career in clinical oncology, combining his translational research in breast cancer with his clinical work as well as conducting clinical trials.

Contact

anthony.kong@cancer.org.uk

Publications

Kong A, Calleja V, Leboucher P, Harris A, Parker P and Larijani B. HER2 oncogenic function escapes EGFR tyrosine kinase inhibitors via activation of alternative HER receptors in breast cancer cells (PLoS One in press 2008).

Kong A, Powell M and Blake P. The role of post-operative radiotherapy in endometrial carcinoma. (Clinical Oncology in press 2008).

Kong A, Simera I, Collingwood M, Williams C and Kitchener H. Adjuvant Radiotherapy for Stage 1 Endometrial Carcinoma: Systematic Review and Meta-analysis. Ann Oncol. 2007;18(10):1595-604.

Hyer S, Kong A, Pratt B and Harmer C. Salivary Gland toxicity following 131I therapy for thyroid cancer. Clinical Oncology 2007; 19(1): 83-6.

Kong A, Leboucher P, Leek R, Winter S, Calleja V, Harris A, Parker P and Larijani B. Prognostic value of an activation state marker for EGFR in tissue microarrays of head and neck cancers. Cancer Research 2006; 66 (5) (featured on Cancer Research Cover).

Kong A, Bridgewater CH, Vilarino-Varela M and Plowman PN. Molecular therapy as primary treatment for adult solid cancers: Gefitinib and Imatinib. CME Cancer Medicine 2004; 2(3): 75-78.

Kong A and Edmonds P. Testosterone therapy in HIV wasting syndrome: systematic review and meta-analysis. Lancet Infect Dis. 2002 Nov; 2 (11):692-9.

Trent S, Kong A, Short SC, Traish D, Ashley S, Dowe A, Hines F, Brada M. Temozolomide as second-line chemotherapy for relapsed gliomas. J Neurooncology 2002; 57(3):247-51.

Oral and poster presentations

  • The AACR Centennial Conference on Translational Cancer Medicine 2008, Monterey, California. Poster presentation.
  • 20th Meeting of the European Association for Cancer Research 2008, Lyon France. Oral presentation.
  • London Research Institute-Barts Symposium 2007. Oral presentation.
  • The National Cancer Research Institute (NCRI) conference 2006 and 2007. Poster presentation.
  • The American Association for Cancer Research (AACR) annual meeting, Washington 2006. Poster presentation.
  • The annual Cancer Research UK Clinical Fellow Meeting 2005. Oral presentation.