Erschienen in:
01.10.2013 | Colorectal Cancer
KRAS Mutations and Rectal Cancer Response to Chemoradiation: Are We Closer to Personalization of Therapy?
verfasst von:
Sunil Krishnan, MD, George J. Chang, MD, MS
Erschienen in:
Annals of Surgical Oncology
|
Ausgabe 11/2013
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Excerpt
Ras is a membrane-bound protein that regulates multiple downstream pathways, including the Raf/MAPK and the PI3K/Akt signaling pathways.
1 When bound to guanosine triphosphate (GTP), it remains in an active state but is inactivated by intrinsic GTPase activity that hydrolyzes GTP to guanosine diphosphate (GDP). Ras is activated by upstream receptor tyrosine kinases, including epidermal growth factor receptor (EGFR), that recruit guanine nucleotide exchange factors (GEFs) to the cell membrane to open up the GTP binding site of Ras. Ras–GTPase then deactivates Ras with the assistance of GTPase activating proteins (GAPs). This intricate balance between activation and deactivation of Ras efficiently regulates the communication of signals arising from receptor tyrosine kinases on the cell membrane to effector molecules in the cytoplasm and nucleus. Mutations in the
KRAS gene disrupt this fine balance. …
