EGFR Mode of Action

01.06.2010

EGFR: Internalisation and Recycling
An active RTK complex can be internalized via endocytosis and sorted to either the lysosomal compartment for degradation, or recycled to the plasma membrane as an inactive RTK. When recycled, the receptor regains ability for growth-factor binding and activation.1

EGFR: Resistance Mutations in NSCLC
Despite initial clinical benefit with first-generation TKIs in NSCLC, insensitivity and/or resistance has been observed. Although there may be multiple mechanisms of resistance, one possible mechanism is the presence of a point mutation in the ATP-binding pocket of EGFR, referred to as the T790M mutation.2 This mutation renders NSCLC tumors unresponsive to first-generation TKIs.2,3,4

References

  1. Wiley HS. Exp Cell Res. 2003;284(1):78-88.
  2. Herbst RS, Heymach JV, Lippman SM. N Engl J Med. 2008;359(13):1367-1380.
  3. Sequist LV. Oncologist. 2007;12(3):325-330.
  4. Inukai M, Toyooka S, Ito S, et al. Cancer Res. 2006;66(16):7854-7858.