The use of bacteria as vectors in tumour treatment

Abstract

U današnje vrijeme tumor je jedan od najčešćih i najraširenijih uzročnika smrti u ljudi. Velikim povećanjem broja oboljelih došlo je i do većeg interesa znanstvenika za razvoj efikasnijih načina liječenja tumora od dugo primjenjivanih radio- i kemoterapije. Povoljno djelovanje nekih bakterijskih bolesti na regresiju tumora bilo je poznato već nekoliko stoljeća, no tek je razvojem genetičkog inžinjerstva ponovno pobuđen interes za bakterije, ovaj puta kao vektore za ciljano liječenje tumora. U ovom radu su predstavljena tri soja bakterija na kojima je rađen najveći broj istraživanja: Bifidobacterium, Salmonella i Clostridium. Svaki soj ima svoje prednosti i nedostatke, ali za sada najviše obećava soj bakterija Clostridium, najviše zbog svoje izrazite anaerobnosti, velike efikasnosti naseljavanja tumora i mogućnosti stvaranja spora. U bakterije se ugrađuju geni za enzime koji će u samom tumoru pretvarati lijekove u aktivan oblik i time smanjiti njihovu sistemsku toksičnost. Do sada su se bakterije pokazale kao učinkovitiji i sigurniji vektori za liječenje tumora u odnosu na virusne vektore. Unatoč uspjehu modelnih pokusa potrebno je još mnogo testiranja i istraživanja prije nego bakterijski vektori prođu sve faze kliničkih studija i uđu u široku upotrebu, no mogli bi značiti prekretnicu u liječenju ne samo tumora nego i ostalih bolesti nedostupnih uobičajenim terapijama.Tumour is one of the most common and the most widely spread cause of death in humans in the modern world. Scientists became more interested in finding a more effective tumour treatment than those commonly used, such as radio- and chemotherapy, with the increase in the number of tumour patients. Although the beneficial effect of some bacterial infections on tumour regression was observed a few centuries ago, the interest in bacteria arose once again with the development of genetic engineering, which led to the use of bacteria as vectors for targeted tumour treatment. Most researches were performed on three genera of bacteria: Bifidobacterium, Salmonella and Clostridium, which are presented in this work. All of these genera have their advantages and disadvantages but the most promising seems to be Clostridium because they are strictly anaerobic, spore forming bacteria with a great capacity to colonize tumours. Bacteria were engineered to express prodrug activating enzyme inside the tumour, thus lowering systemic toxicity induced by the activated prodrug. Engineered bacteria have been shown to serve as a more efficient and safer vector for tumour treatment then the viral vectors. Although bacterial vectors have been shown to be successful in many tumour models, further experiments and researches are necessary for completing all clinical trials and entering a wide use in treating tumour patients. However, bacterial vectors could be a turning point in tumour treatment as well as for other diseases unreachable to conventional therapies