Modulation of VEGF and tumour angiogenesis in endocrine resistant breast cancers
Research team: Molecular Endocrinology Team
Project Summary
Tumour growth and subsequent development of metastases is highly dependent on angiogenesis, a process in which the Vascular Endothelial Growth Factor (VEGF) plays a pivotal role not only as a mitogen for endothelial cells, but also mediating secretion and activation of enzymes involved in degrading the extracellular matrix as well as playing a key role in survival. Evidence suggests that the HER2 and VEGF signalling pathways are interlinked at the molecular level in human breast cancer and hence influence cell proliferation and that VEGF levels are associated with endocrine-resistance.It has been postulated that oestrogens also enhance VEGF expression via interaction of E2 bound ERα with an imperfect ERE within the VEGF promoter. However, the role of ER regulation of VEGF in an acquired endocrine resistant model has yet to be established. Our investigation focuses on the interaction between these pathways at the molecular level and their role in influencing tumour angiogenesis and survival.
Targeting both the VEGF and ER signalling pathways concomitantly may provide enhanced therapeutic benefit. Studies are ongoing to assess the anti-tumour activity of VEGF-R tyrosine kinase inhibitors.
Biography
Dr. Susana Banerjee MA MBBS MRCPDr. Susana Banerjee was awarded a first class for her BA(Hons) degree in Physiology from the University of Cambridge. She completed her medical training at the Royal Free Medical School, University of London in 2000 and was a University Gold Medal Finalist. Susana embarked on a Specialist Registrar in Medical Oncology training programme at the Royal Marsden Hospital in 2004. She was awarded an Avon Clinical Fellowship and joined Prof Mitch Dowsett and Dr. Lesley-Ann Martin’s team at Breakthrough Research Centre in September 2005. Susana has been secretary of the Junior British Oncology Association and is currently the Medical Advisor of the Complementary Medicine Steering Group at Breakthrough. She received the San Antonio Breast Cancer Symposium Novartis Oncology Basic Science Award in 2007. Dr. Banerjee aims to build a career in academic medical oncology and is keen to be actively involved in the design and implementation of clinical trials.
Contact
susana.banerjee@icr.ac.ukPublications
S Banerjee, S Pancholi, R A'hern, Z Ghazoui, I Smith, M Dowsett and LA Martin. The effects of neoadjuvant anastrozole and tamoxifen on circulating vascular endothelial growth factor and soluble vascular endothelial growth factor receptor 1 in breast cancer. Clin Cancer Res. 2008 May 1;14(9):2656-63S Banerjee, M Dowsett, A Ashworth and LA Martin. Mechanisms of disease: angiogenesis and the management of breast cancer. Nature Clinical Practice Oncology 2007; 4:536-50
S Banerjee, J Reis-Filho, S Ashley, D Steele, A Ashworth, S Lakhani and IE Smith. Basal-like Breast Carcinomas: Clinical outcome and response to chemotherapy. J Clin Pathol 2006; 59:729-35
S Banerjee, IE Smith, L Folkerd, J Iqbal, P Barker and M Dowsett. Comparative effects of anastrazole, tamoxifen alone and in combination on plasma lipids and bone-derived resorption during neoadjuvant therapy in the IMPACT trial. Ann Oncol. 2005;16(10):1632
Oral Presentations
The VEGFR inhibitor, PTK787, is also an aromatase inhibitor: preclinical studies30th San Antonio Breast cancer Symposium Dec 2007
The efficacy of neoadjuvant tamoxifen or anastrazole on circulating VEGF levels.
British Breast Cancer Group 99th meeting, Oxford June 2007
