Cancer research is a challenging endeavour, mainly due to the various causal factors and origin of the malignancy. Cells within our body are constantly impacted by external and internal environmental conditions. These conditions can vary depending on the individual’s lifestyle, living environment and underlying genetic makeup.
Cells are programmed to divide, grow and die. If control of cellular proliferation, survival and death is lost, an increased growth of cells results in a lump or mass that can be benign or malignant.
Though one speaks of cancer as if it is one disease, it is actually a group of different diseases not only when it involves different organs but also within the same organ and many times even within the same individual. In an era of personalised treatment, the characterisation of the individual tumour is important so as to tailor the treatment to the particular tumour.
This characterisation has been particularly well established for breast cancer. Analysis of breast tissue is required for definite diagnosis and to determine the type of disease. As early as 1975, the presence of oestrogen receptors on the breast cancer cells gave the oncologist the opportunity of treating the cancer with endocrine blocking drugs. Since then, the pathologist has been able to conduct specific tests (measuring biomarkers) to classify distinct subtypes that have different and unique treatment responses and outcomes.
Today, breast cancer is usually classified into three distinct groups: endocrine positive (presence of oestrogen and progesterone receptors), HER2 positive (the presence of HER2 receptors) and triple negative (the absence of the mentioned receptors). For the first two subtypes, drugs have been developed to target the abnormal protein, hence increasing the successful cure rate.
The era of genomics and proteomics has opened the door to further subtype and thus possibly novel therapeutic targets. Increasing this knowledge on the cause of disease and identifying novel markers to further subtype breast cancer is one of the main objectives of the breast cancer research group at the University of Malta, which I head.
Cancer research is a challenging endeavour
The research group brings together novel scientific knowledge, and adapts cutting-edge technology to develop accurate and reliable tests to classify breast cancer types. The main aim of this group is to define the state of a protein complex that is usually tightly regulated in cells that divide normally.
In specific patients, this protein complex loses its normal activity and an uncontrolled cellular growth is initiated and maintained. Measuring the activity of this complex in tumours is challenging but at the end of a three-year research programme, a panel of gene expression biomarkers were identified and validated. This scientific knowledge was discovered utilising breast cancer cellular models and validated on tissue samples.
By utilising this technique, breast cancer tissues can be easily and quickly classified into the three subtypes, thus reducing the time of diagnosis and confirming ambiguous cases, including heterogeneous samples. The group is currently validating the test on different sources of patient material prior to commercialisation.
Solid tumours are known to release cells or shed vesicles (small parts of cells) or DNA into the blood stream. The identification of these substances in the blood is known as liquid biopsy.
As part of a project financed by the Malta Council for Science and Technology, the designed cancer test will be adapted to be sensitive enough to identify the subtypes in liquid biopsies. This will enable the measurement of solid tumour products in blood as a tool for early diagnosis, to understand the efficacy of treatment and measure resistance and to identify early recurrence.
The same technology is also being utilised to characterise and increase our knowledge of cancers originating from different organs, starting with a colorectal cancer study.
Together with my team, we presented these findings at various prestigious conferences, placing within the top five oral presentations at the 29th European Congress of Pathology in Amsterdam. We also received the JoVE Video Publication Grant, featuring the development of a novel RNA-based multiplex assay to diagnose breast cancer subtypes.
I also coordinated the European Association for Preventive, Predictive and Personalised Medicine congress in Malta, where various initiatives were launched to promote prevention of cancer and early diagnosis.
The achievements of the research group are highly dependent on the vital and invaluable contribution of the consultants at Mater Dei Hospital and Sir Anthony Mamo Oncology Centre and the precious and courageous contribution of the patients through consented samples provided for research purposes. In addition, the various international collaborations, including the Institute of Molecular Medicine in Leeds and the University of St Andres in Scotland, are of great value towards the validation of the scientific findings.
Prof. Godfrey Grech is an associate professor at the University of Malta, heading the Breast Cancer Research Group. The scientific results originate from various projects funded by the Faculty of Medicine & Surgery, the Italy-Malta European Regional Development Fund programme (ImagenX) and scholarships donated through funds raised by the Alive Charity Foundation and Action for Breast Cancer Foundation through the University’s Research Innovation and Development Trust. The validation and application of the accurate test for patient monitoring and early diagnosis is funded through the project ‘Accurate Cancer Screening Tests’, financed by the Malta Council for Science and Technology through Fusion: The R&I Technology Development Programme 2016.