Cypriot scientists have pioneered an innovative strategy designed to revolutionise the treatment of aggressive solid tumours. This novel approach addresses the significant physical and biological obstacles that have historically hindered the effectiveness of cancer therapies. By ingeniously combining established medical interventions, the research has demonstrably improved drug delivery capabilities. Furthermore, preclinical trials have showcased the potential for complete tumour eradication, even in advanced metastatic cases.
Professor Dr. Fotios Bekris and his dedicated team at the Institute’s Department of Genetic, Therapeutic and Ultrastructural Pathology of Cancer led this significant research. Their work, which also benefited from crucial contributions by Dr. Konstantina Neophytou and Dr. Stella Angeli, tackles a critical challenge in oncology. Many aggressive tumours, particularly those like pancreatic cancer, sarcomas, and melanomas, possess a dense and rigid microenvironment. This physiological characteristic obstructs blood flow and oxygen circulation, consequently limiting the penetration of chemotherapy drugs and diminishing the impact of immunotherapies. Moreover, this constrictive environment actively suppresses the tumour's interaction with the immune system, creating a formidable defence against treatment.
To effectively surmount these substantial challenges, the Cypriot researchers have formulated a sophisticated multi-pronged strategy utilising three clinically validated components. Initially, the repurposed antihistamine ketotifen is administered. This readily available medication has proven effective in softening tumour tissue, thereby reducing rigidity and simultaneously enhancing blood flow within the tumour. Complementing this, therapeutic ultrasound is employed to temporarily increase the porosity of the tumour's blood vessels. This transient increase in permeability facilitates a broader and deeper infiltration of therapeutic agents. Finally, standard chemotherapy is administered within this optimised therapeutic environment.
The synergistic impact of these combined interventions results in a remarkable weakening of the tumour's structural integrity. This compromise in structure allows for the unimpeded passage of therapeutic agents into previously inaccessible tumour regions. The research team observed tangible improvements, including a notable reduction in tissue stiffness, enhanced blood perfusion, and a significant decrease in tumour volume within their experimental models.
Crucially, when this refined drug delivery system was integrated with nanotherapy and immunotherapy, the outcomes were truly transformative. Preclinical studies involving breast cancer models demonstrated not only the complete elimination of primary tumours but also the successful eradication of metastatic lesions. This suggests a potent reactivation of the immune system, which, once the tumour microenvironment becomes more permeable, can mount a more effective and sustained attack against cancer cells, potentially fostering long-term immune memory. The significance of this breakthrough is amplified by the fact that the core components of the strategy – ketotifen, therapeutic ultrasound, and standard chemotherapy – are already approved for clinical use. This existing regulatory status could considerably expedite the translation of these findings from the laboratory to patient care, offering a much-needed glimmer of hope for individuals battling aggressive cancers. As medical understanding increasingly points towards the physical accessibility of treatment targets as being as crucial as the potency of the drugs themselves, this Cypriot innovation represents a substantial leap forward in our ongoing fight against this complex disease. The project received substantial backing, with a €1.5 million grant from the European Research Council under the ERC-2022-Starting Grant program, underscoring the international recognition of its potential impact. Collaborators from the Cancer Biophysics Laboratory at the University of Cyprus also played a pivotal role in the project's success, led by Professor Dr. Triantafyllos Stylianopoulos.