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The relay that turns cytokine signals into gene changes. Overactive in blood cancers (JAK2 in myelofibrosis), it is also the wire that carries interferon's cancer-killing message, so tumours cut it to escape immunotherapy.
Cytokine receptors recruit JAK kinases that phosphorylate STAT transcription factors. JAK2 V617F drives myeloproliferative neoplasms (ruxolitinib, fedratinib, momelotinib approved); STAT3 is a hub for IL-6-driven survival, immunosuppression, and cachexia; STAT5 in leukaemias. Interferon-γ signalling via JAK1/2-STAT1 upregulates MHC and PD-L1; JAK1/2 loss-of-function mutations cause acquired resistance to PD-1 blockade. Direct STAT3 inhibitors (degraders, antisense) are in early trials.
JAK-STAT is a doorbell wired to the house lights. Cytokines ring, JAK flips the switch, STAT turns on the lights. Cancers either jam the switch on (JAK2 mutation) or cut the wire so interferon cannot turn on the 'I am infected' lights.
One pathway page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
This paper is the molecular sequel to the 2002 inflammation and cancer review and the basis for IL-6, JAK-STAT and NF-kB directed strategies in cancer as well as for aspirin and other anti-inflammatory prevention trials.
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.
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