Prečo sú mitochondrie vhodné ciele pre liečbu rakoviny

English version

Authors: Z. Tatarkova; S. Kuka; M. Petras; P. Racay; J. Lehotský; D. Dobrota; P. Kaplán
Authors‘ workplace: Department of Medical Biochemistry, Jessenius Faculty of Medicine, Comenius University, Martin, Slovak Republic
Published in: Klin Onkol 2012; 25(6): 421-426
Category: Reviews

Táto práca bola podporená projektom „Centrum excelentnosti pre výskum v personalizovanej terapii“ (CEVYPET), ITMS: 2622012053, spolufinancovaným zo zdrojov EÚ a Európskeho fondu regionálneho rozvoja, a grantom VEGA 1/0028/11 Ministerstva školstva a vedy Slovenskej republiky.

Obdrženo: 2. 12. 2011
Přijato: 31. 5. 2012

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Obdrženo: 2. 12. 2011
Přijato: 31. 5. 2012

Overview

Nové trendy v liečbe rakoviny sa spájajú s rozvojom presne cielených terapeutík, s účinkom na rakovinové bunky a zameraním na špecifické biologické dráhy. Úloha onkoproteínov a tumor-supresorových proteínov v proliferačnej signalizácii, regulácii bunkového cyklu a pozmenenej adhézii je už dobre preskúmaná. Chemické látky, vírusy a žiarenie sú tiež všeobecne prijímanými faktormi, ktoré vyvolávajú mutácie v génoch kódujúcich proteíny súvisiace s tvorbou rakoviny. Nedávne experimenty ukázali, že existujú dva nové kľúčové faktory pôsobiace na proliferujúce bunky – hypoxia a nedostatok glukózy. Tieto môžu iniciovať a podporovať proces malígnej transformácie v malom množstve buniek, ktorým sa podarilo uniknúť bunkovému starnutiu. Neregulovaná bunková proliferácia vedie k tvorbe bunkovej masy presahujúcej svoje rezervy, čo znižuje množstvo kyslíka a živín. Vzniknutý stav hypoxie iniciuje ďalšie kľúčové úpravy, ktoré umožňujú prežitie nádorových buniek. Proces apoptózy je potlačený a metabolizmus glukózy pozmenený. Nedávne experimenty naznačili, že vyčerpanie zásob kyslíka stimuluje mitochondrie, aby spracovávali väčšie množstvá reaktívnych foriem kyslíka (ROS). Aktivujú sa tak signálne dráhy, ako je hypoxiu-indukujúci faktor 1, ktoré podporujú prežívanie nádorových buniek a rast nádorov. Mitochondrie sú čoraz častejšie považované za kľúčové organely podieľajúce sa na chemoterapii, a preto je dôležité nájsť spôsob ako aktivovať apoptózu v mitochondriách za podmienok hypoxie, určiť vzťah medzi mitochondriami, ROS signalizáciou a procesmi aktivujúcimi prežívanie buniek. Každé nové zistenie môže otvoriť cestu pre pochopenie a odhalenie podstaty rakoviny a následné vytvorenie na mieru šitej terapie.

Kľúčové slová:
mitochondria – bunková smrť – energetický metabolizmus – bunková transformácia

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