ULOGA METFORMINA U TERAPIJI NESITNOĆELIJSKOG KARCINOMA PLUĆA

  • Jelena Ljubičič Medicinski fakultet Univerziteta u Beogradu, Beograd, Republika Srbija
  • Andrej Pešić Klinika za hematologiju, Univerzitetski klinički centar Srbije, Beograd, Republika Srbija
  • Kasja Pavlović Klinika za endokrinologiju, dijabetes i bolesti metabolizma, Univerzitetski klinički centar Srbije, Beograd, Republika Srbija
  • Sonja Misirlić Denčić Institut za medicinsku i kliničku biohemiju, Medicinski fakultet Univerziteta u Beogradu, Beograd, Republika Srbija
  • Anđelka Isaković Institut za medicinsku i kliničku biohemiju, Medicinski fakultet Univerziteta u Beogradu, Beograd, Republika Srbija
Ključne reči: karcinom pluća, metformin, klinička studija, molekularni mehanizam

Sažetak


Nesitnoćelijski karcinom pluća (NSCLC) sačinjava 80-85% svih dijagnostikovanih formi karcinoma pluća. Konvencionalni terapijski modaliteti pokazuju malu uspešnost u lečenju  uznapredovalih formi bolesti, što dovodi do razvoja novih lekova koji bi zajedno sa klasičnim hemioteraputicima pobošljali odgovor na postojeću terapiju. Jedan od takvih terapeutika je i antidijabetik metformin koji je pokazao obećavajuće rezultate tokom pretkliničkih i retrospektivnih studija. U ovom radu analizirane su prospektivne kliničke studije koje su ispitivale efekat lečenja karcinoma pluća pomoću metformina i konvencionalnih terapijskih pristupa, kao i pretkliničke studije koje opisuju mogući mehanizam dejstva metformina objavljene u PubMed bazi podataka u prethodnih 10 godina. U pojedinim prospektivnim kliničkim studijama uočene su naznake da terapija metforminom dovodi do poboljšanja opšte stope preživljavanja i produžetka perioda bez progresije bolesti. Međutim, ovakve studije su malobrojne i karakteriše ih nedovoljan broj ispitanika kao i smanjena komplijantnost prema terapiji metforminom. Pretkliničke studije ukazuju na citotoksični efekat metformina prema ćelijama NSCLC, aktivaciju apoptoze, kao i sinergizam sa radioterapijom, hemioterapeuticima i biološkom terapijom koja se primenjuje, ali su pokazani mehanizmi dejstva upitni uzimajući u obzir visoke koncentracije metformina koje se primenjuju in vitro. Na osnovu dostupnih podataka nije moguće sa sigurnošću proceniti da li metformin dovodi do poboljšanja efekta lečenja u poređenju sa konvencionalnim terapijskim pristupima, niti doneti jasan zaključak o ćelijskim mehanizmima kojima bi se ovakav efekat ostvario. Stoga je neophodno da buduća pretklinička istraživanja budu bolje dizajnirana u smislu mogućnosti translacije rezultata na in vivo okolnosti, a kliničke studije bolje kontrolisane kao i da obuhvate veći broj precizno odabranih ispitanika.

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