IN VITRO INVESTIGATION ON THE EFFECTS ON CANCER CELLS OF TUMOR TREATING FIELDS AND A COMBINED THERAPY OF A NOVEL CHEMOTHERAPY AGENT WITH MAGNETIC NANOPARTICLES.

Introduction In recent decades, medical research has been primarily focused on the inherited aspect of cancers, despite the reality that only 5–10% of tumors discovered derive from genetic causes. Cancer is a broad term, and it is therefore not accurate to address it as a purely genetic disease. Understanding cancer cells’ behavior is the first step in countering them. Behind the scenes, there is a complicated network of environmental factors, DNA errors, metabolic shifts, and electrostatic alterations that build over time and lead to the illness’ development. Every cell in the human body possesses electrical properties that are essential for proper behavior both within and outside of the cell itself. It is not yet clear whether these changes correlate with cell mutation in cancer cells, or only with their subsequent development. New therapies targeting or using these electrical properties are developed and tested every year to enhance the possibilities of survival and the conditions of the patients. This thesis is focused on two different therapies that affect, directly or indirectly, the electrostatic environment of the cell and more precisely the mitotic spindle and the formation of the microtubules. Materials and Methods One is the application of a new promising therapy, Tumor Treating Fields (TTFs), on HeLa cells stably expressing m-Cherry-H2B and EGFP-tubulin. TTFs are a non-invasive therapy that utilized a low-intensity alternating electric field with an intermediate frequency range (50-300kHz). While the second one is the combination of the established targeting therapy concerning the use of magnetic nanoparticles with static magnetic fields and a new chemotherapy drug, CR42-24, on different cancer and non-cancer cell lines. Results A much longer mitotic spindle, together with a strong viability reduction, was observed in the cells exposed to TTFs giving rise to new hypotheses on the functioning of this treatment. A consistent improvement of cytotoxicity of the CR42-24 was achieved with the combined therapy mostly on cancer cell lines. Conclusions These results suggest that a much better understanding is needed to fully recognize the anti-cancer power of TTFs and that the combined therapy can become a reliable improvement of the chemotherapy alone, following a necessary enhance.