ROLE OF ANGIOGENESIS IN TUMOR PROGRESSION Angiogenesis inhibitors therapy: From promising experimental animal models to reality of clinical use
Autori:
Natalija Dedić Plavetić, Tomislav Letilović, Damir Vrbanec
Sažetak
Sažetak. Razvoj novih krvnih žila važan je u rastu primarnog tumora i u procesu metastaziranj a. Tumorske stanice mogu aktivirati mirujuće endotelne stanice te dovesti tako do stvaranja novih krvnih žila. Razumijevanje molekularnih mehanizama uključenih u taj proces ključno je za razvoj antiangiogenih lijekova. Antiangiogena terapija trebala bi dopuniti konvencionalne terapijske protokole. Klasična kemoterapija usmjerena je prema tumorskim stanicama koje su genski nestabilne te kao takve sklone razvijanju rezistencije, dok je antiangiogena terapija usmjerena prema genski stabilnim endotelnim stanicama. Preliminarni pretklinički rezultati pokazali su da endotelne stanice ne razvijaju rezistenciju te da antiangiogena terapija može dovesti do zaustavljanja rasta tumora. Novija klinička istraživanja pokazala su ograničenja angiogene terapije, no kombinirana primjena antiangiogenih lij ekova i klasične kemoterapije poboljšava rezultate konvencionalnih terapij skih protokola za diseminiranu bolest.
Summary
Summary. The development of new blood vessels (angiogenesis) is necessary to sustain the growth of primary tumor as well as a process of tumor metastasis. Cancer cells activate the quiescent vasculature to produce new blood vessels via an »angio- genic switch«. Understanding of molecular mechanisms involved in that process is essential for the development of antiangiogenic drugs. Drugs that inhibit angiogenesis could offer a treatment that is complementary to traditional chemotherapy. Chemotherapy directly targets tumor cells, which are prone to develop acquired drug resistance due to genetic instability. Antiangiogenic therapy is directed against endothelial cells in tumor stroma, which are genetically stabile. First results from animal studies supported the theory that endothelial cells do not develop drug resitance and had excellent results in inducing tumor quiescence. However, recent clinical trials showed that antiangiogenic therapy has limitations but that it can improve conventional thera- peutic modalities of disseminated disease.
