What led you to the idea of focusing your research on developing new strategies to improve cancer therapies?
“In solid tumours, cancer cells grow very fast and start to push the surrounding host tissue to expand further. At the same time, the host tissue exerts reciprocal pressure on the tumour to compress it. This combination of mechanical forces results in tumor stiffening and compression of blood vessels in the tumour, which in turn hampers effective drugs delivery. In many types of pancreatic and breast cancer, and sarcoma, 80% of the blood vessels are not functional anymore. This may seem positive as, without oxygen carried by blood, the tumour could die. But cancer cells bypass this mechanism and instead invade other tissues and organs, thereby developing metastasis.
My idea focusses on intervening at the vascular level to re-establish blood flow to the tumour, so drugs can easily reach cancer cells and kill them.
For example, in chemotherapy, drugs circulate throughout the entire body, causing damage to the immune system and other organs, while only a tiny amount reaches the tumour. If we manage to open the compressed vessels, we obtain a dual benefit: significantly increasing the amount of drug reaching the tumour and at the same time lowering the drug dosage administered to the patient, thereby considerably reducing adverse effects.
With the support of an ERC Starting Grant, we have discovered a method to restore vascular flow in tumors.”
What specific approach did you apply?
“During our research, we observed that repurposing commonly used drugs, such as some antihistamines - which do not have many adverse effects – can diminish the mechanical forces exerted between the tumour and the surrounding host tissue. This reduction in mechanical forces leads to a more regular blood flow within the tumour. As a result, our approach involves administering the antihistamine to patients before treating them with chemotherapy or immunotherapy, or a combination of both. We have successfully tested this methodology in multiple preclinical studies and currently it is being tested here in Cyprus for people affected by sarcoma.
It takes time to see the long-term therapeutic effects in patients. By the end of my ERC Proof of Concept project in March 2024, we hope to have the first results. I am very happy to see our progress, starting from the very beginning and now reaching the stage of conducting clinical trials.”
How did you continue once you had this outcome?
“Not all tumours are the same; they manifest distinct physiology and characteristics. Even a single tumour can undergo changes over time. This means that not all patients need to be treated with antihistamine.
Through the ERC Consolidator Grant, I went a considerable step further by designing a methodology to screen patients who would benefit from a pre-treatment to improve blood perfusion before undergoing immunotherapy.
Our proposal involved monitoring the mechanical characteristics of tumours, specifically stiffness and blood perfusion, using ultrasound imaging. So far, tumour classification predominantly relies on molecular markers that reflect their biological characteristics. There are no markers that specifically capture the mechanical properties of tumours. To address this limitation, we have developed mechanical markers that can be obtained via medical imaging. These novel markers will help classify the patients into responders or non-responders to anticancer therapy.
In the case of non-responders, our approach involves first administering antihistamine treatment. Once the vessels regain proper function, the subsequent treatment for cancer can start. In cooperation with two oncology centres in Cyprus, we are currently applying this know-how to translational trials, aiming to validate and implement this novel methodology in a clinical setting.
Building upon our progress, we have secured additional funding through another ERC Proof of Concept grant. With this support, we are using advanced Artificial Intelligence methods to develop a software tool that aims to analyse both molecular and mechanical markers, enabling a more complete assessment of the tumour characteristics. This tool will speed up the screening of patients and help oncologists in making informed decisions."
What do you regard as your most significant achievement?
“I was excited to see the success of my hypothesis in pre-clinical settings, demonstrating the effectiveness of intervening to reduce tumour stiffness and improve vascular function. This breakthrough has the potential to improve the treatment outcomes for patients with cancer, particularly for those with hard-to-treat cancers. (article 1, article 2)
The support I received from the ERC has been pivotal in driving my research forward. The timing was particularly fortuitous as I had recently relocated from the USA to Cyprus, only to encounter a collapsed economy with very limited funding for research. However, thanks to the ERC Starting Grant, in 2014 I was able to establish my research team and purchase state-of-the-art equipment.
Moreover, I would like to add that the most effective approach to research in my field involves the combination of different disciplines. In my lab, engineers and tumour biologists work together, leveraging their unique expertise to tackle complex challenges. This interdisciplinary synergy aligns seamlessly with the type of research that the ERC is keen on supporting.”
What is the next step in your research?
“My ambition is to convert my Cancer Biophysics lab into a centre of excellence to strengthen our ongoing collaborations with other European countries, the USA and Japan. Cyprus being one of the Widening countries in Horizon Europe, provides funding opportunities to create such a centre and partner with leading institutions and oncology centers from Cyprus and abroad.
My vision for this centre extends beyond research alone; it also involves providing education and fostering collaboration between researchers and oncologists. The invaluable insights gained from the translational trials and the accumulated know-how will not only improve cancer healthcare in the island but also across Europe and the whole Eastern Mediterranean region.”
Triantafyllos Stylianopoulos is an Associate Professor and the Head of the Cancer Biophysics Laboratory at the University of Cyprus. He received a Diploma in Chemical Engineering from National Technical University of Athens, Greece (2003) and a PhD also in Chemical Engineering from the University of Minnesota, USA (2008). Subsequently, he performed his post-doctoral training at the Department of Radiation Oncology at Harvard Medical School and Massachusetts General Hospital (2008-2010). Prof. Stylianopoulos has co-authored numerous peer-reviewed articles in the fields of biomechanics, drug delivery, cancer nanomedicine and tumor microenvironment. He is the beneficiary of a Starting grant, a Consolidator grant and three Proof of Concept grants.