Signal‐transduction inhibitors in renal cell carcinoma

Signal transduction in cancer cells is a complex process that involves receptor tyrosine kinases (RTKs) that in turn trigger cytoplasmic kinases. There are many cellular signalling pathways that work independently, in parallel, and/or through interconnections, to promote cancer development, growth and survival. The three major signalling pathways in cancer cells include the phosphatidyl inositol-3-kinase (PI3K)/AKT, protein kinase C (PKC), and mitogen-activated protein kinase (MAPK)/Ras-Raf-MEF-ERK signalling cascades. Cancer cells show ‘oncogene addiction’, in that they depend for survival on one pathway. In clear cell RCC that pathway seems to be the VEGF/PDGK/PI3K/AKT/mTOR/ S6/HIF pathway, as clinical trials have shown that highly selective or specific blocking of the kinases involved in this signalling pathway has been associated with major responses and a survival advantage.

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