Versterking van de anti-kanker immuunrespons door modulatie van longkankercellen en de tumor micro-omgeving met behulp van Auranofin.

Despite the discovery of new therapeutic strategies, lung cancer still accounted for more than 18% of the cancer-related deaths in 2018. P53 is the most frequently mutated gene in lung cancer and is often associated with an unfavorable therapeutic outcome. In our search for new anticancer therapies, we discovered that Auranofin (AF), an old drug currently used for rheumatoid arthritis, is highly effective against mutant p53 expressing cancer cells. The drug is a selective inhibitor of the antioxidant thioredoxin reductase. Previous studies have shown that AF dependent inhibition of this antioxidant blocks several pro-tumorigenic pathways. Recent findings have shown that these pathways are also involved in attracting immunosuppressive cells to the tumor microenvironment and in hiding cancer cells from immune cells. To date, little is known about the underlying mechanisms by which AF induces cancer cell death and if AF can modulate the immune suppressive tumor microenvironment. We hypothesize that AF can induce immunogenic cell death, a type of cell death that alerts the patient's immune system leading to an antitumor immune response. In addition, we will study the in vivo effect of AF on different types of immune cells inside the tumor to determine if AF is a potential candidate for combination strategies with immunotherapy.

Keywords:OXIDATIVE STRESS, ONCOLOGY, IMMUNOLOGY, CELL FATE

Disciplines:Cancer biology, Cancer therapy