Vascular disrupting effect of electrochemotherapy

učinki na žilje tumorja

Abstract

The therapeutic potential of targeting the tumor blood supply is now well acknowledged. Vascular targeted therapies target tumor blood vessels. The research and development have resulted in a variety of investigational agents, among which many are currently being clinically tested. Two distinct groups of vascular targeted therapies have evolved, anti-angiogenic and vascular-disrupting approach. They differ in several aspects: their physiological target, the type and extent of the disease which is likely to be susceptible to one or the other group of therapies, and their treatment scheduling. Besides the direct cytotoxic effect of electrochemotherapy on tumor cells, recent discoveries have detected also its vascular-disrupting effect. Due to vascular damage, abrogation of tumor blood flow, and consequently, of tumor ischemia, a cascade of tumor-cell deaths is induced. Therefore, electrochemotherapy is effective in the treatment of bleeding metastases due to its vascular disrupting effect; it quickly stops bleeding and reduces tumor burden.

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Povzetek

Terapevtska učinkovitost zdravljenj, ki delujejo na žilje tumorja, je sedaj splošno priznana. Odkrivajo se vedno nova zdravila in pristopi, ki ciljajo žilje tumorja, zato jih imenujemo žilno ciljano zdravljenje (vascular targeted therapies). Poznamo dve vrsti tega zdravljenja, in sicer antiangiogeno (anti-angiogenic therapies) in žilno razdiralno (vascular-disrupting therapies). Ločita se po fizioloških tarčah, primernosti za zdravljenje glede na obseg bolezni in režimu zdravljenja. Zadnja odkritja kažejo, da ima elektrokemoterapija poleg neposrednega citotoksičnega delovanja tudi žilno razdiralni učinek, ker na endotelne celice tumorskega žilja deluje citotoksično. Zaradi odmiranja teh celic prihaja do trajnih ustavitev pretoka krvi in do ishemičnega propada tumorskih celic v poškodovanih delih tumorja. Zaradi žilno razdiralnega učinka je elektrokemoterapija učinkovita tudi pri zdravljenju krvavečih tumorskih lezij, kar se kaže v takojšnji ustavitvi krvavitve in v poznejšem zmanjšanju tumorske lezije.