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

 * 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: PMID 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