For this year’s ongoing research on breast cancer we met up with a medical laboratory scientist, and team leader at the laboratory of Molecular Pathology & Genetics, Pathology Department (Mater Dei Hospital), Dr. Jeanesse Scerri, who obtained her PhD at the University of Malta in 2019. For the past eight years she specialised in personalised cancer medicine and she has collaborated with international cancer research groups and also a member of the EU4Health Action Grant: CAN.HEAL: Cancer Diagnostics & Treatment for All; Genomics for Public Health.
Personalised medicine involves a tailor-made approach to disease treatment, based on specific disease and patient characteristics, to ensure the most effective treatment with the least side effects.
In cancer, this entails looking for genetic changes (mutations) that make the tumour more susceptible to specific drugs, and targeting it with these drugs. For example, Herceptin® was developed and has now been used for many years specifically for breast cancers that express a protein on their cell surface called HER2. These are known as HER2-positive tumours.
This type of targeted therapy is especially important in clinically advanced cases, where the tumour is either too big to be surgically removed or has already spread to other parts of the body. The main challenge of targeted therapies is that cancer, being a constantly evolving population of cells, tries to evade the actions of drugs (such as Herceptin) by acquiring mutations and activating pathways that make it resistant to the treatment. For example, this would be seen as a relapse in the patient treatment, with tumour that was being effectively treated observed to grow again on imaging.
In other cases, although the tumour would express HER2, it would already have co-occurring mechanisms that still make it resistant to Herceptin from the beginning; this is known as intrinsic resistance.
This study, which formed part of her PhD research and was funded through RIDT, involved the generation of a HER2-positive breast cancer cell line with acquired resistance to Herceptin® (SKBR3-T15), to study its mechanisms of resistance. The findings were compared to those of a commercially available cell line, JIMT-1, that is also HER2-positive but shows intrinsic Herceptin® resistance.
For this purpose, over 100 proteins involved in biological pathways of cellular growth and survival were measured using an innovative technique called DigiWest at the Natural and Medical Sciences Institute (NMI), University of TĂĽbingen, Germany. This showed that the two types of resistance are brought about by different mechanisms.
As a potential future clinical application, the involved proteins could be measured in patients’ tumours to either predict their initial response to Herceptin® or for continuous monitoring during treatment for acquired resistance. This study was supervised by Prof. Christian Scerri & Prof. Godfrey Grech. The paper is available online.
A very important aspect of personalised medicine is that of continuous monitoring. For solid tumours like breast cancer, this is currently done by regular imaging; however, tests cannot be made on the tumour tissue by imaging alone, and regular biopsies would be too invasive as they involve surgical procedures. Liquid biopsy is an exciting solution: cancers are known to shed some of their cells, DNA and other particles into the bloodstream; thus, from a simple blood draw, one can isolate these cancer-specific particles and carry out specific tests to monitor for resistance. The last part of the PhD research focused on this exciting new technique which is being further developed by the research group at the University of Malta.
“Basic research is the foundation of healthcare.Although we might take the availability of such an enormous repertoire of medicines for granted, and be rightfully disappointed with the lack of available treatment for some diseases, each medicine that is put on the shelf has undergone years and years of research, starting from basic research such as this, to uncover mechanisms of disease, through the development of drugs targeting a specific pathway that has gone wrong, to rigorous clinical trials that assess the efficacy and the safety of the final products.” says Dr Scerri.
She continues by emphasising that “Research is impossible without funding – this project was made possible thanks to a generous donation by ALIVE Charity Foundation to the University of Malta Research Trust, RIDT. Also, collaboration with international research groups is key, especially for small countries such as Malta but in reality, for any country, because expertise that is lacking in one lab can be sought in another.
The scientific community is all about sharing knowledge, which is what journal publications are for.”
This Pink October, our message is to join the other advocates for breast cancer prevention in stressing the importance of regular self-checking and screening. Despite the advances in personalised medicine, early detection followed by surgery is still the best determinant of a good outcome and the best chance for cure. If you have any questions about breast cancer screening, kindly email the National screening centre.