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The breakthrough comes from the Institute’s Department of Genetic, Therapeutic and Ultrastructural Pathology of Cancer, led by Professor Dr. Fotios Bekris. The findings, recently published in the peer-reviewed journal Journal of Controlled Release, introduce a novel way to overcome one of oncology’s most persistent challenges: getting drugs to actually reach tumor cells.
The barrier that protects yumors
Many solid tumors, such as pancreatic cancer, breast cancer, sarcomas, and melanomas, develop a dense, rigid microenvironment composed of connective tissue and abnormal blood vessels. This structure acts as a physical and biological barrier, severely limiting blood flow, oxygen delivery, and drug penetration. As a result, chemotherapy and even immunotherapy often fail, not because the drugs are ineffective, but because they cannot access the tumor in sufficient amounts.
The same barrier also suppresses immune activity, preventing immune cells from entering tumors and carrying out their cancer-killing functions.
A combination approach using approved tools
To address this problem, the research team designed a strategy that combines three clinically established components. First, they repurposed the approved antihistamine ketotifen, previously shown by the group to soften tumor tissue and improve blood circulation. This was paired with therapeutic ultrasound, which temporarily increases the permeability of tumor blood vessels. Standard chemotherapy was then administered alongside these interventions.
Together, these methods weakened the tumor’s defensive structure, allowing drugs to reach regions that had previously been inaccessible.
Significant tumor reduction and immune activation
The researchers observed that this approach led to reduced tissue stiffness, improved blood perfusion, and a marked decrease in tumor size. Building on earlier work by the same group, the team has also shown that combining this strategy with nanotherapy and immunotherapy can completely eliminate tumors in preclinical breast cancer models, including metastatic disease.
Importantly, once the tumor microenvironment becomes more accessible, the immune system is reactivated. This not only enhances treatment effectiveness but also promotes long-term immune memory against cancer.
Implications for future cancer care
Because the approach relies exclusively on drugs and techniques that are already approved for clinical use, the findings could accelerate translation into patient care. The research supports a growing shift in oncology: successful cancer treatment depends not only on how powerful a drug is, but on whether it can physically reach its target.
Funding and collaboration
The project was funded by a €1.5 million grant from the European Research Council under the ERC-2022-Starting Grant program. Key contributors included Dr. Konstantina Neophytou and Dr. Stella Angeli, along with collaborators from the Cancer Biophysics Laboratory at the University of Cyprus, led by Professor Dr. Triantafyllos Stylianopoulos.
