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.
- Böhm S et al. Neoadjuvant chemotherapy modulates the immune microenvironment in metastases of tubo-ovarian high-grade serous carcinoma. Clinical Cancer Research, in press. 2016
- Gopinathan G et al. Interleukin-6 stimulates defective angiogenesis. Cancer Res. 2015; 75 (15) 3098-107
- Milagre CS et al. Adaptive upregulation of EGFR limits attenuation of tumor growth by neutralizing IL-6 antibodies with implications for combined therapy in ovarian cancer. Cancer Res. 2015;75(7):1255-64
- Rei et al. Major contribution of gamma delta T cells to IL-17A production and ovarian cancer cell growth in vivo. Immunology; 140, 160-160
- Castellano et al. Requirement for interaction of PI3-kinase p110α with RAS in lung tumor maintenance. Cancer Cell. 2013;24(5): 617-30
- Archibald et al. Sequential genetic change at the TP53 and chemokine receptor CXCR4 locus during transformation of human ovarian surface epithelium. Oncogene. 2012; 31(48):4987-95
Who does the research
- Cancer Research UK
- Leukaemia and Lymphoma Research
- Pancreatic Cancer Research Fund