Apoptosis as a target of "smart medicines" for malignancy

Apoptoza je oblik stanične smrti neophodan organizmu za njegov razvoj i održavanje stanične homeostaze. To je proces u kojem stanica aktivno pokreće svoju vlastitu smrt zbog različitih fizioloških ili patoloških procesa. Apoptoza je vrlo složen i dobro kontroliran proces i za organizam je veoma važno njezino pravilno odvijanje. U tumorski stanicama dolazi do poremećaja kontrolnog mehanizma zbog čega stanice postaju rezistentne na apoptozu. Rezistentnost na apoptozu predstavlja veliki problem u razvoju ciljane antitumorske terapije. U ovom radu prikazano je nekoliko lijekova s različitim mehanizmom djelovanja iz skupine „induktora apoptoze“. To je nova skupina „pametnih lijekova“ koja inducira apoptozu ili vraća sposobnost tumorskim stanicama za odvijanje iste. Lijekovi koji ciljaju stanične mete uključene u proces apoptoze mogu djelovati na: 1) protein p53, 2) Bcl-2 porodicu receptora, 3) inhibitore apoptoze, 4) kaspaze, 5) proteasom i 6) receptore smrti. Njihova velika prednost je ciljano djelovanje samo u tumorskim stanicama. Većina ovih lijekova trenutno je u različitim fazama predkliničkih i kliničkih ispitivanja. Trenutna istraživanja pokazuju da većina njih u predkliničkim testiranjima pokazuje odlične antitumorske učinke, no u testiranjima na animalnim modelima ili kliničkim ispitivanjima na ljudima taj je učinak puno slabiji. Uglavnom pokazuju sinergističko djelovanje u kombiniranoj terapiji. Ciljana terapija moduliranja procesa apoptoze predstavlja novo poglavlje u antitumorskoj terapiji od koje se očekuju sve bolji rezultati u skoroj budućnosti.Apoptosis is a form of cell death necessary for the development of an organism and maintenance of cell homeostasis. It is a process in which a cell actively initiates its own death due to various physiological and pathological processes. Apoptosis is a very complex and well controlled process, the regularity of which is extremely important for the organism. The control mechanism is disrupted in tumour cells, which is why cells become resistant to apoptosis. The resistance to apoptosis is a large issue in the development of targeted anti-tumour therapy. This paper presents several medicines with different mechanisms of action pertaining to the group of “apoptosis inducers”. This is a new group of “smart medicines” that induces apoptosis or restores the ability of tumour cells for this process. Medicines aiming at cell targets included in the apoptosis process can affect the following: 1) protein p53, 2) Bcl-2 receptor family, 3) inhibitors of apoptosis, 4) caspases, 5) proteasome, and 6) death receptors. Their great advantage is the targeted action solely in tumour cells. Most of these medicines are currently in different stages of pre-clinical and clinical testing. Current researches show that most of them show excellent anti-tumour effects in pre-clinical tests, but tests on animal models or clinical tests on humans showed a much weaker effect. They mostly show a synergistic effect in combined therapy. The targeted therapy of modulating the apoptotic process is a new chapter in anti-tumour therapy, from which increasingly improved results are expected in near future