Scientists from the University of Wrocław have demonstrated that cancer cells can be chemically ‘programmed’ to take up drugs used in targeted therapies, potentially allowing treatment to be directed towards cancer cells rather than healthy ones.
The process developed by a team led by Professor Łukasz Opaliński from the Faculty of Biotechnology of the University of Wrocław makes it possible to regulate the mechanism by which a drug is taken up by a cell, both from outside and inside the cell.
The research has been published in the Journal of the American Chemical Society. According to the university, most of the experimental work was carried out under Opaliński’s supervision by early-career scientists from the university: doctoral candidates Aleksandra Chorążewska and Krzysztof Ciura, and Natalia Porębska, PhD.
The Wrocław team collaborated with researchers from the Hirszfeld Institute of Immunology and Experimental Therapy PAS, the Wrocław Medical University, and Goethe University Frankfurt.
Modern targeted therapies such as antibody-drug conjugates (ADCs) and protein-drug conjugates (PDCs) are based on identifying an antigen that is highly expressed in a tumour but minimally expressed in normal tissue. A cytotoxic agent is then delivered to the cancer cell through a process known as endocytosis.
In practice, however, finding such ‘perfect targets’ for targeted therapies is extremely difficult. For some types of cancer, it has so far proven impossible, the university reports.
Researchers from Opaliński’s team and their collaborators have demonstrated that ‘instead of searching for a unique antigen, it is possible to take control of the drug uptake mechanism - regulating it simultaneously from both outside and inside the cell’.
The approach involves synchronously controlling cell biology in two ways: from outside the cell, using the geometry of an antigen-recognizing molecule, and from inside, through precise pharmacotherapy with inhibitors.
This could make it possible to incorporate into cancer therapy molecular targets that were previously considered non-selective or even ‘inaccessible to drugs’.
‘In the future, this could enable the treatment of cancers for which modern targeted therapies are currently unavailable (such as pancreatic cancer) due to the lack of specific molecular targets’, says Aleksandra Chorążewska, a researcher from the University of Wrocław, quoted in the university press release.
Professor Łukasz Opaliński said that translating this technology to clinical practice would require further research.
‘However, the presented results open up an extremely promising avenue for the development of multimodal targeted therapies’, he added. (PAP)
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