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A chain of proteins that passes a message from the cell surface to the nucleus, each one switching on the next like a relay race. Cancer drugs try to break a link in the chain.
A typical pathway runs receptor, adaptor, small switch protein (RAS), kinase cascade (RAF, MEK, ERK), transcription factor, gene; the PI3K-AKT-mTOR pathway runs in parallel and controls growth and survival. Pathways branch, feed back on themselves, and cross-talk, so blocking one link often leads the cell to reroute the signal, which is a major cause of drug resistance and the rationale for combining drugs that hit two points. Each pathway page on this site shows the chain, the mutations that jam it on, and the drugs that hit each node.
Almost every targeted therapy on this site, from trastuzumab and EGFR inhibitors to ALK, MET, RET and FGFR drugs, acts on the receptors this review describes. It is the mechanistic background for understanding both why these drugs work and why resistance mutations arise.
The JAK-STAT pathway explains how interferon and interleukin signals act in immunity and cancer. Its discovery underlies ruxolitinib and other JAK inhibitors in myeloproliferative neoplasms, the role of STAT3 in tumour-promoting inflammation, and the interferon-gamma signalling that determines whether tumours respond to checkpoint inhibitors.
Shares Dario C. Altieri, Growth signal, Kinase, Drug resistance (primary and acquired).
Shares Phosphorylation, Kinase.
Shares Growth factor, Receptor.
Shares Darnell, Kerr and Stark 1994: JAK-STAT pathways and transcriptional activation by interferons, Receptor.
Shares Oestrogen receptor signalling, Wnt / β-catenin, PI3K / AKT / mTOR, RAS / RAF / MEK / ERK (MAPK).
Shares Androgen receptor signalling, Drug resistance (primary and acquired), PI3K / AKT / mTOR.
Shares Androgen receptor signalling, Drug resistance (primary and acquired), PI3K / AKT / mTOR.