Olga Oikonomidou: Clinical Translational Research in Breast Cancer
Breast cancer is the most common cancer in women worldwide with more that 1.1 million women diagnosed annually. The pre-operative setting (neo-adjuvant chemotherapy) could provide an opportunity to study the impact of systemic therapies on breast cancer biology. As a research tool neo-adjuvant chemotherapy is useful because of the availability of tumour response as an end point and the availability of tissue for biopsy and biomarker development.
It is impossible to identify early during treatment those patients whose tumours will respond and those who will gain no apparent benefit in that their cancer either does not reduce appreciably, or even increases in size. There is an urgent need to determine on an individual basis whether treatment is producing a worthwhile effect. Treatments are not without undue toxicity and continuing with a therapy that is not beneficial reduces the potential to introduce other treatments.
With the advent of gene expression profiling it is now possible to analyse thousands of genes using small tissue samples from patient’s tumours. The predictive value of tumour phenotypes incorporating thousands of genes offers a more comprehensive approach for predicting response and benefit to treatment compared to testing a single gene. Thus we hypothesize that comprehensive molecular profiling of clinical samples, both diagnostic and on treatment may reveal alterations that are associated with drug resistance, metastatic recurrence and disease progression. Therefore we will be able to better characterize those cancers that receive insufficient benefit from current therapies and predict which alternate therapies and drug combination strategies may cure those patients that do not respond to current therapies. With the bioinformatics provided by Dr Andy Sim’s group (Richard Bownes PhD student, Dr Arran Turnbull PostDoc) we will able to interpret these changes to better understand the molecular mechanisms determining breast cancer response to treatment with the aim of bringing these findings into the clinical practice.
Also in recent years a wealth of information indicating the potential use of circulating DNA for cancer screening, prognosis and monitoring of the efficacy of anticancer therapies has emerged. Detecting cfDNA in plasma or serum could serve as a 'liquid biopsy', which would be useful for numerous diagnostic applications and would avoid the need for tumour tissue biopsies. Use of such a liquid biopsy delivers the possibility of taking repeated blood samples, consequently allowing the changes in cfDNA to be traced during the natural course of the disease or during cancer treatment. cfDNA yields are higher in patients with malignant lesions than in patients without cancer. The events that lead to the increase of cfDNA during cancer development and progression are still not well understood. However, recent data has shown that analyses of circulating DNA allow the detection of tumour-related genetic alterations that are relevant to cancer development and progression. DNA methylation which tends to occur in specific regions of the DNA called CpGs might be a better way compared to gene mutations which can be spread over very large regions of its sequence, to evaluate sequence changes in cell free circulating DNA. Since DNA methylation is reflected within cfDNA, we are currently working on the detection of breast cancer-specific DNA methylation changes in breast cancer patients’ plasma (Professor Tim Aitman’s group: Dr Fiona Semple and Dr Gil Thomas).
Finally, the use of efficient strategies to isolate cfDNA provides valuable insights into tumour biology. The challenges associated with conventional cfDNA extraction methods prevent their further clinical applications. We are working on the development of a novel microfluidic separation method to rapidly and efficiently isolate cfDNA from breast cancer patients (Dr Nicholas Leslie’s group).
Dr Oikonomidou holds a position as an Academic Consultant Medical Oncologist with special interest in breast cancer at the Edinburgh Cancer Research Centre, University of Edinburgh. She obtained her first degree BSc (Hon) in Human Genetics from the University of Leeds. This was followed by a MSc in Oncology and Cellular Pathology from the same University. She received her Medical Degree from the Medical School of Athens, Greece. After successfully completing a MRes in Immunology (Distinction) and a PhD (Distinction) in Biochemistry and Pathophysiology in Medical School of Athens, Greece, she started her training as a Medical Oncologist at the Naval Hospital of Athens. Three years later she moved to London to work as a specialist registrar in King’s College Hospital and Guy’s and St Thomas’ Hospital of London where she stayed for 3 years. On completion of her training she moved to Edinburgh where she worked as a Senior Clinical Research Fellow at the Cancer Research Centre of the University of Edinburgh for 2 years before she has taken up her post as an Academic Consultant Medical Oncologist with special interest in breast cancer. Her responsibilities are split equally between running a busy breast oncology clinic in the Western General Hospital and leading on breast cancer translational studies. Dr Oikonomidou is an active member of several professional societies including ACP, ESMO, ASCO and EORTC. She is actively involved in numerous clinical trials and she is the local Principal Investigator in several clinical trials. She is the Chief Investigator in a number of translational studies. Regular teaching and research supervising commitments both at the undergraduate and postgraduate level are also included in Dr Oikonomidou’s academic role.