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Cancer-related Inflammation

Why we focus on Cancer-related Inflammation

Cancer-related inflammation is an important process contributing to malignant disease, with common and defined factors at different stages of progression. Until recently, the field has been driven by the hypothesis that extrinsic inflammatory pathways promote or, in some cases, initiate cancer i.e. that inflammation causes or promotes cancer. However, there is now evidence that there is an intrinsic inflammation pathway, activated by genetic events that cause neoplasia, i.e. cancer causes inflammation. Activation of oncogenes such as myc, ras and ret, or inactivation of tumour suppressors, such as pVHL, leads to constitutive production of inflammatory cytokines and chemokines by the initiated cell. Oncogene and tumour suppressor pathways are proven intracellular targets for therapies, but these recent data mean that inflammatory cytokines, and their receptors, are potential extracellular targets for the development of new drugs. These targets include TNF-α, IL-1β and IL-6, with different cytokines being implicated as major factors in different cancer models.

What we do

  • We investigate the hypothesis that cancer-related inflammation can alter immunity, angiogenesis, disease promotion, progression and response to therapy.
  • The underlying mechanisms are deregulated and represent potential therapeutic targets to modify responses in cancer. 
  • We are conducting early phase clinical trials of new agents targeted against the key drivers of cancer associated inflammation.

Key Publications

  • Kulbe et al. A dynamic inflammatory cytokine network in the human ovarian cancer microenvironment. Cancer Research 2012; 72: 66-75.
  • Maniati et al. Crosstalk between the canonical NF-κB and Notch signaling pathways inhibits Pparγ expression and promotes pancreatic cancer progression in mice. J Clin Invest 2011; 121(12): 4685-99.
  • Coward et al. Interleukin-6 as a therapeutic target in human ovarian cancer. Clin Cancer Res. 2011; 17: 6083-96.
  • Schioppa et al. B regulatory cells and the tumor-promoting actions of TNF-α during squamous carcinogenesis. Proc Natl Acad Sci USA 2011; 108: 10662-7.
  • Saadi et al. Stromal genes discriminate preinvasive from invasive disease, predict outcome, and highlight inflammatory pathways in digestive cancers. Proc Natl Acad Sci USA 2010; 107: 2177-82.
  • Charles et al. The tumor-promoting actions of TNF-alpha involve TNFR1 and IL-17 in ovarian cancer in mice and humans. J Clin Invest 2009; 3011-3023.
  • Li et al. A novel function of colony-stimulating factor 1 receptor in hTERT immortalization of human epithelial cells. Oncogene 2009; 28: 773-80.
  • Hagemann et al. Re-educating tumor-associated macrophages by targeting NFκB signalling. J Exp Med 2008; 1261-1268.

Who does the research

→ Click here for BCI senior researchers working on cancer-related inflammation.

Major Funders

  • Cancer Research UK
  • Leukaemia and Lymphoma Research
  • MRC
  • Pancreatic Cancer Research Fund