Temsirolimus의 기작과 임상

목차

1. mTOR pathway
2. mTOR inhibitor
3. Temsirolimus
4. Clinical trial
5. Adverse effect

본문내용

The main pathway leading to activation of mTOR is through PI3K and Akt, a protein kinase.

Signaling through the PI3K / Akt pathway can be started by binding of growth factors to their receptors in the cell membrane. These receptors include insulin-like growth factor receptors (IGFR), platelet-derived growth factor receptor (PDGFR), vascular endothelial growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR), and the HER family.

Downstream, mTOR controls the translation of specific messenger RNA by activating S6K and cyclin-dependent kinases (CDKs) leading to formation of proteins that are necessary for cell division.

The mRNA regulated by mTOR are templates for ribosomal proteins and proteins that regulate the G0-G1 cell cycle transition, such as cyclin D1, and VEGF.

One additional protein whose levels are increased when mTOR is activated is hypoxia inducible factor (HIF)-1 which is expressed in RCC cells mTOR regulates the translation of transcripts for hypoxia-inducible factor alpha subunits, which are commonly elevated in renal carcinomas, particularly clear cell carcinomas. HIF overproduction is associated with increased VEGF, a hallmark of renal carcinoma

참고 자료

S. Chan Cancer Reserch UK (2004)
S. Vignot Annals of Oncology (2005)
Hadoux J. Renal cell carcinoma: focus on safety and efficacy of temsirolimus (2010)
Kapoor A. Inhibition of mTOR in kidney cancer (2009)
Hadoux J. Renal cell carcinoma: focus on safety and efficacy of temsirolimus (2010)
Stephen M. Ansell. Low-Dose, Single-Agent Temsirolimus for Relapsed Mantle Cell Lymphoma (2008)
Dimitrios Zardavas. Temsirolimus Is Highly Effective as Third-Line Treatment in Chromophobe Renal Cell Cancer (2011)