What is KRAS?

KRAS is a downstream component of the EGFR signaling network. EGFR regulates cancer-cell proliferation, apoptosis and tumor-induced neoangiogenesis

KRAS links growth promoting signals from the cell surface to the nucleus. It is a member of the RAS protein group of GTP/GDP binding proteins.
- KRAS acts as a molecular switch, functionally characterized by the change from an inactive GDP-binding state to an active GTP-binding state
- GTP-bound RAS can interact with more than 20 effector proteins (including RAS, PI3-K and RalGDS)
- The switch to a GTP-binding form normally occurs transiently when growth factor receptors (such as EGFR) are activated.

However, when specific mutations in KRAS occur, the resulting KRAS protein can be constitutively active (it can then function independently of upstream growth factor receptor driven signals and remain active).

Anti-EGFR monoclonal antibodies (cetuximab and panitumumab) are available for the treatment of patients with metastatic colorectal cancer (mCRC), however their clinical treatment efficacy is limited to a subset of patients: EGFR-independent, constitutive activation of the RAS pathway impairs response to anti-EGFR drugs.
- Activating mutations in the KRAS gene can predict resistance to anti-EGFR monoclonal antibodies in mCRC patients
- These mutations are found in approximately 40% of tumors of mCRC patients and are almost always detected in codons 12 and 13 of exon
- For this reason KRAS mutation testing is necessary for mCRC patients before treatment with anti-EGFR therapy.

More information on KRAS mutations in colorectal cancer:

Last changed: 2017-02-03