**NICOSIA, CYPRUS** – A pioneering strategy developed by Cypriot researchers promises to revolutionise the treatment of aggressive solid tumours by surmounting the formidable physical and biological barriers that have long hampered therapeutic efficacy. The innovative approach, recently detailed in the *Journal of Controlled Release*, combines established medical interventions to significantly enhance drug delivery and, in preclinical trials, has demonstrated the capacity for complete tumour eradication, even in cases of metastatic disease.
The research, spearheaded by Professor Dr. Fotios Bekris and his team at the Institute’s Department of Genetic, Therapeutic and Ultrastructural Pathology of Cancer, with significant contributions from Dr. Konstantina Neophytou and Dr. Stella Angeli, addresses a critical bottleneck in cancer therapy. Many aggressive tumours, including notoriously difficult-to-treat cancers such as pancreatic cancer, sarcomas, and melanomas, are characterised by a dense, rigid microenvironment. This physiological obstacle impedes the circulation of blood and oxygen, consequently restricting the penetration of chemotherapy drugs and limiting the effectiveness of immunotherapies. Furthermore, this constrictive environment can actively suppress the tumour’s interaction with the immune system, creating a formidable defence against treatment.
To circumvent these challenges, the Cypriot researchers have devised a multi-pronged strategy that leverages three clinically validated components. Firstly, the repurposed antihistamine ketotifen is employed. This readily available medication has been shown to soften the tumour tissue, thereby alleviating some of the rigidity, and simultaneously improving blood flow within the tumour. Complementing this, therapeutic ultrasound is utilised to temporarily increase the porosity of the tumour’s blood vessels. This transient enhancement in permeability allows for a broader and deeper ingress of therapeutic agents. Finally, standard chemotherapy is administered within this optimised environment.
The synergistic effect of these interventions is a remarkable weakening of the tumour's structural integrity. This structural compromise facilitates the unimpeded passage of therapeutic agents into areas of the tumour that were previously inaccessible. The research team observed tangible improvements, including a notable reduction in tissue stiffness, enhanced blood perfusion, and a significant decrease in tumour volume in their experimental models.
Crucially, when this refined drug delivery system was integrated with nanotherapy and immunotherapy, the results were nothing short of transformative. Preclinical studies involving breast cancer models showed not only 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.