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The review that laid out how inflammation contributes at every stage of cancer, from the DNA damage that starts it to the signals that help it grow and spread, and named the molecular switches, such as NF-kB and STAT3, that connect immune cells to tumour cells.
Grivennikov, Greten and Karin reviewed the roles of inflammation in tumour initiation, promotion, progression and metastasis. Chronic inflammation from infection, autoimmunity or environmental irritants produces reactive oxygen species and cytokines that damage DNA and stimulate proliferation; tumour-promoting inflammation acts through transcription factors NF-kB and STAT3 and cytokines such as IL-6, TNF and IL-1; and inflammation also supports angiogenesis and metastasis while suppressing anti-tumour immunity. They noted that a substantial share of cancers, on some estimates up to a fifth, is linked to chronic infection or inflammation.
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.
Together with the 2002 Nature review this essay put inflammation on the cancer research agenda; the tumour-associated macrophage and IL-6 work that followed, and the aspirin prevention trials, trace back to it.
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 Interleukin-6 and IL-6 receptor, Balkwill and Mantovani 2001: inflammation and cancer, back to Virchow?, Coussens and Werb 2002: inflammation and cancer, Enabling characteristic: tumour-promoting inflammation.
Shares Darnell, Kerr and Stark 1994: JAK-STAT pathways and transcriptional activation by interferons, Inflammation.
Shares Balkwill and Mantovani 2001: inflammation and cancer, back to Virchow?, Inflammation.
Shares JAK-STAT signalling, Inflammation & NF-κB.
Shares JAK-STAT signalling, Inflammation & NF-κB.
Shares Coussens and Werb 2002: inflammation and cancer, Inflammation.
Shares Enabling characteristic: tumour-promoting inflammation, Inflammation & NF-κB.