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Position in a signalling chain: upstream proteins send the message, downstream proteins receive it. A mutation downstream of a drug's target can make the drug useless.
In the RAS-MAPK pathway, the EGFR receptor is upstream of RAS, which is upstream of RAF, MEK and ERK; the nucleus is the far downstream end. The direction matters for treatment because blocking an upstream protein does nothing if a downstream one is already stuck on: EGFR antibodies fail in colorectal cancers with KRAS mutations because KRAS sits below EGFR and fires regardless. The same logic explains why resistance so often emerges downstream of a drug target and why combination therapy sometimes pairs an upstream and a downstream inhibitor.
In plain words · A growth receptor that is mutated in some lung cancers and overproduced in others; the first great success of targeted pills.
Showing the target this term concerns: EGFR.
Shares Growth signal, Signalling pathway, Kinase, PI3K / AKT / mTOR.
Shares Growth signal, Signalling pathway, Kinase, PI3K / AKT / mTOR.
Shares Growth signal, Signalling pathway, RAS / RAF / MEK / ERK (MAPK), EGFR.
Shares Growth signal, Kinase, BRAF, EGFR.
Shares Growth signal, PI3K / AKT / mTOR, BRAF, RAS / RAF / MEK / ERK (MAPK).
Shares BRAF, RAS / RAF / MEK / ERK (MAPK), EGFR.