Open Access

Gabriella Melo-Zainzinger

• There has been a substantial evolution of anti-cancer therapies in the last decade, leading to improved prognosis and disease-free survival of patients with melanoma. Due to the number of patients that still develop resistance or to the high systemic toxicity and side effects, new treatment options are still needed. Regardless of the type of therapeutic interventions (except surgery), the reactive oxygen species (ROS) are a by-product or contribute to the action mechanism of many successful therapies. In this context, medical cold atmospheric plasma (CAP) arises as a promising tool, and studies are important to prove the effectiveness of this new device. Since combination therapies are the current standard way to treat melanoma, we explored candidates to be combined with cold atmospheric plasma, with potential to become a therapeutic option in the combination. Here, we tested the radiotherapy and clinically safe mitochondrial inhibitor drugs. In the end of the study, both, ionizing radiation and four mitochondrial-targeted-drugs showed to be promising candidates for the combination with CAP. These combinations induced increased cytotoxicity and modulated the immune system improving the anti-tumor immune response. Mitochondrial damage seems to be the first stage to induce cellular deficiency and culminate in apoptotic cell death. Furthermore the release of GM-CSF contribute to a pro inflammatory state and immune system activation. This dissertation showed that CAP serves as an excellent tool to boost melanoma cell death and induce anti-tumor response. In addition, in our proposed therapeutic combination, the intensity of plasma treatment could be decreased possibly resulting in less systemic toxicity. Our results serves as model to be studied in other tumor entities.