NOVI BIOMARKERI ZA PRIMJENU USMJERENOG LIJEČENJA IMUNOTERAPIJOM U KARCINOMU ENDOMETRIJA

Endometrial cancer (ED) is the most common malignancy of the female reproductive system and the fourth most common cancer in women in the developed world. In the past decade, the incidence of ED has increased by 2.4% and mortality by 1.9% per year. This failure in prevention and treatment rests in part on the fact of a poor understanding of the heterogeneity and biodiversity of this malignancy. The Cancer Genome Atlas Research Network provides a new classification of ED which defines four subgroups of cancers based on their genetic characteristics. The integration of their knowledge into the existing classification seems necessary to create an optimal diagnostic and prognostic classification. Ultramutated tumors with a large number of somatic mutations within the polymerase epsilon exonuclease domain (POLE) and hypermutated tumors with microsatellite instability (MSI) are two subgroups of the ED with significant expression of PD-1 (programmed death-1) and its ligand PD-L1 (programmed death ligand-1). Pharmacological inhibition of the PD-1 / PD-L1 pathway enables reactivation of the immune response against the tumor and therefore reduces tumorinduced immune suppression. This hypothesis has shown successful clinical outcomes in other types of malignancies such as non-small cell lung cancers, melanoma, kidney, and bladder cancers. Nivolumab and pembrolizumab, both monoclonal antibodies to the PD-1 lymphocyte receptor, give solid preliminary results in ED immunotherapy and significantly lower cytotoxicity than standard adjuvant therapy.