Radiation Oncology/Radiobiology/Growth Factors

Growth Factors ErbB Family of 4 receptor tyrosine kinases ErbB-1 (EGFR) ErbB-2 (her2) ErbB-3 ErbB-4 Transmembrane proteins, existing as monomers at surface When a ligand binds, dimerisation arm becomes untethered, and the proteins dimerize Tyrosine kinase activity EGFR thumb|right Ligands: Epidermal growth factor (EGF): produced by platelets, macrophages, salivary glands, kidneys Transforming growth factor alpha (TGF-α): produced by macrophages, brain cells, keratinocytes HB-EGF, Amphiregulin, betacellulin, epigen, epiregulin: produced by various cells around the body Review: 15142631, Herbst R, IJROBP 2004 EGFR Pathways EGFR -> Ras -> Raf -> MEK -> MAPK -> myc -> transcription EGFR -> Ras -> Raf -> MEK -> MAPK -> RSK -> S6 -> transcription EGFR -> PI3K -> AKT -> mTOR PTEN PTEN gene encodes a phosphatase, which uses PIP-3, which is also produced by PI3K above. Loss of PTEN therefore increases PIP-3 levels, leading to inappropriate AKT activity, and subsequent protection of cancer cells from apoptosis PTEN is a tumor suppressor PTEN loss confers resistance to EGFR inhibitors Please see PTEN Hamartoma Tumor Syndrome