mTOR signaling pathway and mTOR inhibitors in the treatment of cancer

Abstract

Mammalian target of rapamycin (mTOR) plays a major role in the regulation of protein translation, cell growth, and metabolism. Three basic signalling pathways that have been described as important in cancer including the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR kinase cascade, the protein kinase C (PKC) family, and the mito­gen-activated protein kinase (MAPK)/Ras signalling cas­cades. mTOR has been defined as a key kinase acting downstream of the activation of PI3K/AKT. These path­ways are frequently deteriorated in cancer, and therefore mTOR inhibition is a important antitumor target. mTOR inhibitors include rapamycin (i.e. sirolimus) and its deriva­tives; temsirolimus, everolimus, ridaforolimus and defo­rolimus. mTOR inhibitors has the important potential to provide anticancer activity in many tumor types.

Keywords

• PI3K/AKT/mTOR, mTOR inhibitors, cancer

Kanser tedavisinde mTOR sinyal yolağı ve mTOR inhibitörleri

Abstract

mTOR (Rapamisin protein kompleksinin memeli hedefi) hücre büyümesi ve metabolizmasında önemli role sahip­tir. Kanserde önemli olduğu saptanan üç temel sinyalizas­yon yolu; (PI3K)/AKT kinaz zinciri, protein kinaz C ailesi (PKC) ve mitojenle aktive olan protein kinaz (MAPK)/Ras vardır. mTOR; PI3K/AKT sinyal yolağının akış aşağı akti­vasyonunda anahtar bir kinazdır. Bu yolaklar sıklıkla kan­serde bozulur ve bu yüzden de mTOR önemli bir antitü­mör hedeftir. Antikanser ajanlar olarak mTOR inhibitörleri rapamisin ve ondan türetilmiş temsirolimus, everolimus ve ridaforolimus sonradan deforolimus oluşturmaktadır. mTOR inhibitörleri birçok kanser tipinde önemli bir hedef­tir.

Keywords

• PI3K/AKT/mTOR, mTOR inhibitörle­ri, kanser

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