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