Therapeutic potential of epigenetic active substances in neoplastic disease treatment

Abstract

Neoplastične bolesti drugi su najčešći uzrok smrti u svijetu, odmah nakon kardiovaskularnih bolesti. Visoka smrtnost uvjetovana je, pored ostalog, nedovoljno uspješnom konvencionalnom antitumorskom terapijom. Stoga se i dalje ulažu veliki napori kako bi se pronašli novi terapijski pristupi, posebice u okviru kemoterapije. Mnogi znanstvenici smatraju da su budućnost onkološke terapije lijekovi koji mogu modulirati ekspresiju gena poput epigenetički aktivnih tvari. Taj se novi pristup pokazao uspješnim u liječenju hematoloških zloćudnih bolesti, dočim rezultati niza istraživanja ukazuju na mogućnosti kliničke uporabe epigenetičke terapije u pacijenata sa solidnim tumorima, bilo samostalno bilo u kombinaciji s konvencionalnom terapijom. Međutim, još uvijek postoje prepreke za široku primjenu epigenetičkih lijekova. Uglavnom su to potencijalne nuspojave posebice zloćudna transformacija de novo. Pored toga, za pojedine epigenetički aktivne tvari s poznatim terapijskim učinkom još uvijek postoji problem farmakološke formulacije lijeka koja bi im omogućila maksimalni terapijski potencijal. Znanstvena istraživanja, pored otkrivanja novih lijekova, upozoravaju na sporedne epigenetičke učinke čitavog niza lijekova koji su odavno u primjeni. Iako ove spoznaje naglašavaju nepoznavanje ili čak ignoriranje sveobuhvatnog učinka pojedinih lijekova, također ukazuju na mogućnost alternativne primjene pojedinih lijekova u onkološkoj terapiji. Pored ispitivanja poznatih lijekova, izniman se napor ulaže u identifikaciju epigenetički aktivnih tvari prisutnih u svakodnevnoj prehrani kao vrijednim izvorom prirodnih supstanci s potencijalnim protutumorskim djelovanjem i potencijalom primjene u onkološkoj prevenciji i terapiji budućnosti.Neoplastic diseases are the second leading cause of death in the world, following cardiovascular diseases. A high mortality rate is the result of, among other things,insufficiently effective conventional cancer treatment. Therefore, great effort is still being put into finding new therapeutical approaches, especially in the domain of chemotherapy. Many scientists regard drugs which can modulate gene expression, such as epigenetic active substances, as future of oncologic therapy. The new approach was found to be successful in treating hematological malignancies, while the results of numerous research point to the possibility of clinical application of epigenetic therapy, both inidividually and in combination with conventional therapy. However,there are still obstacles to wide utilization of epigenetic drugs. Mostly, those are potential side effects of epigenetic drugs, especially de novo malignant tranformation. Furthermore, there are still difficulties with reaching pharmacological formulation of some epigenetic active substances with known therapeutic effect, which is vital in order for the drug to reach its full therapeutic potential. In addition to discovering new medicines, scientific research often warn about the secondary epigenetic effects of a number of medicines that have long been in use. Although these insights emphasize the fact that the overall effect of some medications is not known, or is sometimes even ignored, they also point to the possibility of an alternative application of some medicines in oncologic therapy. Along with testing new medicines, a significant effort is put into identifying epigenetic active substances present in daily diet as a significant source of natural substances with potential antitumor impact and a great potential for application in oncologic prevention and therapy of the future