Oncogenic Signalling Research Group
Research Group Head
The focus of the Oncogenic Signalling Laboratory is the identification and characterisation of cellular networks that promote the survival and/or growth of cancer cells.
The team is particularly interested in receptors found on the cell surface that convert external messages to internal signals that promote uncontrolled cellular growth, a hallmark of cancer cells. Once a receptor important to cancer cells has been identified, Professor Johns and his team endeavour to develop antibodies that block the function of the receptor. This specific form of treatment is known as targeted therapy. Depending on the receptor being targeted, blocking its function may induce growth arrest, cell death or sensitisation to other agents such as chemotherapeutics. This research has an emphasis on glioma (brain cancer) but also has implications for a wide variety of cancers, including colon, breast, lung, and head and neck cancers.
Targeted therapies are considered by the research and clinical communities as the best option for developing new therapies for cancer. However, this approach will only be effective if we understand how the different signalling pathways within individual tumour types, or sub-types, interact.
The Oncogenic Signalling Research Group is currently undertaking the following:
- Developing novel antibodies that target signalling pathways (e.g. the EGFR, c-Met, IL-6 and IL-13Ralpha2 signalling pathways) that are critical for glioma growth and invasion
- Determining how many signalling networks need to be targeted to achieve robust inhibition of a broad range of gliomas
- Characterising the types of mutant EGFR and other receptor tyrosine kinasesand their signalling pathways
- Providing new insight into cross-talk between signalling pathways relevant to glioma
- Identifying mechanisms of resistance to EGFR-targeted therapies and strategies to overcome these mechanisms
- Developing new treatments for diffuse intrinsic pontine glioma (DIPG), an incurable childhood brain cancer.
Overall, this work will lead to new therapeutic strategies to treat glioma and DIPG, diseases for which there is currently no effective treatment.
The research group is an integral part of the Brain Cancer Discovery Collaborative.
Horne AW, Skubisz MM, Tong S, Duncan WC, Neil P, Wallace EM, Johns TG (2014) Combination gefitinib and methotrexate treatment for non-tubal ectopic pregnancies: a case series. Hum Reprod 29:1375-1377.
Tebbutt N, Pedersen MW, Johns TG (2013) Targeting the EGFR family in cancer: couples therapy. Nat Rev Cancer 13:663-673.
Greenall SA, Gherardi E, Liu Z, Donoghue JF, Vitali AA, Li Q, Murphy R, Iamele L, Scott AM, Johns TG(2012) Non-agonistic bivalent antibodies that promote c-Met degradation and inhibit tumor growth and others specific for tumor related c-Met. PLoS ONE 7:e34658.
Cvrljevic AN, Akhavan D, Wu M, Martinello P, Furnari FB, Johnston AJ, Guo D, Pike L, Cavenee WK, Scott AM, Mischel PS, Hoogenraad NJ, Johns TG (2011) Activation of Src induces mitochondrial localization of the de2-7EGFR (EGFRvIII) in glioma cells: implications for glucose metabolism. J Cell Sci 124:2938-2950.
Pillay V, Allaf L, Wilding A, Donoghue J, Court NW, Greenall S, Scott AM, Johns TG (2009) The plasticity of oncogene addiction: implications for targeted therapies directed to receptor tyrosine kinases. Neoplasia 11:448-458.
Garrett TPJ, Burgess AW, Gan HK, Luwor RB, Cartwright G, Walker F, Orchard SG, Clayton AHA, Nice EC, Rothacker J, Catimel B, Cavenee WK, Old LJ, Stockert E, Ritter G, Adams TE, Hoyne PA, Ward CW, Wittrup D, Chao G, Cochran JR, Luo C, Lou M, Huyton T, Xu Y, Fairlie WD, Yao S, Scott AM, Johns TG (2009) Antibodies specifically targeting a locally misfolded region of tumor associated EGFR. Proc Natl Acad Sci USA 106:5082-5087.