Teoretický prehľad epigenetických zmien a ich možné využitie pri liečbe duktálneho adenokarcinómu pankreasu

Pancreatic ductal adenocarcinoma ranks among the most aggressive cancers with a dismal prognosis and high mortality rate. Nonspecific symptoms, intricate diagnostics, and strong resistance to antitumor therapy hinder the path to successful treatment. Epigenetics, a relatively new research area, is capable to identify key tumorigenic pathways and metastasis-related molecular mechanisms. The reversibility of epigenetic changes harbors a great potential for epigenetic reprogramming as a new therapeutic strategy. Inhibition of DNA methyltransferases and histone deacetylases, which are highly expressed in malignant cells, shows various antitumor effects in preclinical settings, such as induction of apoptosis, cell cycle arrest, reduction of cell migration and sensitization of resistant tumor cells towards treatment. Several phase I and II clinical trials address the efficacy and tolerability of epigenetic drugs in monotherapy or combination regimens for the treatment of solid tumors. Although first- and second-generation inhibitors resulted rarely in promising response rates for pancreatic cancer, third-generation inhibitors together with the identification of new predictive biomarkers could contribute to improving the survival of patients with this insidious disease.This work was funded by the Scientific Grant Agency grant VEGA 2/0052/18, by the Horizon 2020 project No. 857381 VISION and the ERA-NET TRANSCAN-2 project NExT