termsTerm
Downstream and upstream
aka downstream, upstream, downstream of, upstream of, downstream signalling, downstream signaling, downstream effector, downstream effectors, downstream target, downstream targets
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.
Category
Biology basics