Pomen hipoksije pri obsevanju The importance of hypoxia in radiation therapy

Abstract

Uspešnost zdravljenja z radioterapijo (RT) je odvisna od številnih dejavnikov, med katerimi je tudi oksigenacija tumorskih celic. Tumorske celice, ki so dobro preskrbljene s kisikom, so namreč na obsevanje tudi do 3-krat bolj občutljive kot hipoksične tumorske celice. Poleg tega deluje hipoksija v tumorjih kot selekcijski pritisk, zaradi katerega preživijo le bolj maligne celice, z manjšim apoptotskim potencialom. V prisotnosti hipoksije se povečata genomska nestabilnost in metastatski potencial tumorskih celic, zveča pa se tudi odpornost celic na kemoterapijo, kar vse vpliva na uspešnost zdravljenja z RT. Hipoksija je posledica neskladja med celičnim dihanjem, koncentracijo kisika v krvi in perfuzijo tumorja, pri čemer so najpogostejši patogenetski mehanizmi neustrezna ožiljenost, motena difuzija kisika ter anemija, ki je lahko posledica rakave bolezni ali zdravljenja. Z uporabo invazivnih in novejših neinvazivnih diagnostičnih metod lahko ocenimo delež hipoksičnih celic v tumorju in temu prilagodimo terapevtski pristop. Boljši učinek obsevanja slabše oksigeniranih tumorjev lahko dosežemo z uporabo radiosenzibilizatorjev, z izboljšanjem tumorske oksigenacije, s selektivnim uničenjem hipoksičnih celic s citotoksini ter z obsevanjem hipoksičnih predelov z višjimi obsevalnimi odmerki ob pomoči radioprotektorjev in z uporabo sodobnih obsevalnih tehnik.

Abstract (Eng)

The success of radiation therapy (RT) treatment depends on numerous factors, one of which is also tumour cell oxygenation. Tumour cells which are well-supplied with oxygen can be up to 3 times more sensitive to radiation than hypoxic tumour cells. In addition, hypoxia functions as selective pressure in tumours, which results in the survival of only more malignant cells with diminished apoptotic potential. Presence of hypoxia increases the genomic instability and metastatic potential of tumour cells, while also increasing cell resistance to chemotherapy, all of which affects the success of treatment with RT. Hypoxia is a result of an imbalance between cellular respiration, concentration of oxygen in the blood and tumour perfusion, with the most common pathogenic mechanisms being inappropriate vascularization, disturbed oxygen diffusion and anaemia which may be a consequence of cancer or treatment. Using invasive and most recent non-invasive diagnostic techniques, we can assess the proportion of hypoxic cells in the tumour, adapting the therapeutic approach accordingly. A better effect of irradiation of less oxygenated tumours can be achieved using radio sensitizers, by improving tumour oxygenation, through selective destruction of hypoxic cells, and with irradiation of hypoxic areas using higher doses of radiation and with the help of radio protectors or using modern irradiation techniques.